Tributes to Yuan-Cheng Fung on His 90th Birthday

The following sections are included:

• CONTENTS

• PREFACE

Soft tissues rheology is determined by their internal structure and by their constituents' properties and mutual interactions. Specifics of these relationships are analyzed in terms of four constitutive properties: 1) The tissues' non-linear stress-strain relationship is consistent with their collagen fibers non-uniform undulation and gradual straightening with stretch. Response anisotropy is attributed to the fibers non-uniform orientation distribution. 2) The fibers gradual recruitment is also consistent with the tissues' viscoelastic non-linearity. It is shown that under protocols where no fibers buckle (e.g., stress relaxation and creep tests) the fibers recruitment process is compatible with the quasi-linear viscoelastic theory. 3) Preconditioning adaptation of tissues to its loading is an essential response feature, induced by the preconditioning properties of the fibers. The latter are both strain and time dependent. Excellent fit to data of multiple uniaxial (tendon) and biaxial (skin) data is obtained only if preconditioning is incorporated into the constitutive formulation. 4) Residual stress in unloaded state stems from three levels of interactions between the tissues' constituents (the micro, meso and macro levels, respectively), which must all be relieved if a true stress-free reference is desired. In summary, modeling based on structural consideration provides mechanistic insights and facilitates reliable constitutive formulation.

Knowledge of mechanical properties of stress fiber (SF), a bundle of actin filaments, is crucial for understanding its role in mechanotransduction in adherent cells. Here, we characterized tensile properties of single SFs by in vitro manipulation. SFs were isolated from cultured vascular smooth muscle cells with a combination of low ionic-strength extraction and detergent extraction and were stretched until breaking. The breaking force of the SFs for stretching was, on average, 377 nN, which was greater than actin filaments, 600 pN. The Young's modulus was estimated as 1.45 MPa, which was three orders of magnitude lower than actin filaments. Strain-induced hardening, a common mechanical behavior of living adherent cells, was observed in a physiological strain range of the force-strain curves. Estimated force level of physiological tension in single SFs was the same order of magnitude with that of the substrate traction force of adherent cells required for maintenance of cell integrity. These results suggest that SFs are a principal subcellular component in bearing intracellular stresses.

The existence of residual stresses within biological tissues was demonstrated more than two decades ago by Professor Y. C. Fung (1984) when blood vessels sprang open with a longitudinal cut. This simple experiment has been repeated in many load-bearing tissues including articular cartilage. It is believed that these residual stresses and strains play important physiologic roles in functionally reducing the stress in situ. In the present study, the in vitro swelling and curling behaviors of thin strips of cartilage were analyzed with a model using the triphasic mixture theory with a collagen-proteoglycan solid matrix composed of a three-layered laminate with each layer possessing a distinct set of orthotropic properties. A cone-wise linear elastic matrix has been incorporated to account for the well-known tension-compression nonlinearity of the tissue. It has already been shown that this theory can account for the curvatures found in published experimental results. The results suggest that for a charged hydrated soft tissue, such as articular cartilage, the balance of proteoglycan swelling and the collagen restraining within the solid matrix is the origin of the in situ residual stress, and that the layered collagen ultrastructure, e.g., relatively dense and with high stiffness at the articular surface, play key roles in determining curling behaviors of such tissues.

Blood flow and associated fluid shear stress play a role in the regulation of vascular morphogenesis during embryonic development and adaptive alterations in response to physiological and pathological stimuli. Various flow patterns, including laminar and vortex flow, in association with different levels of fluid shear stress are present in the vascular system. As fluid shear stress negatively regulates the mitogenic activities of vascular cells and molecular transport processes in the circulator system, nonuniform shear stress exerts profound effects on the formation of thrombus and neointima. In this study, we showed, by using an experimental model of polymeric cylinder implantation to the rat vena cava, that fluid shear stress controlled the development of thrombus and neointima. The degree of thrombus/neointima development was inversely correlated to the shear stress level, resulting in the formation of thrombus/neointima with a shear stress-dependent geometry and size. Furthermore, shear stress gradients controlled smooth muscle cell migration from the host-vessel media to the thrombus/neointima via the mediation of cell density gradients established under the influence of nonuniform shear stress. This paper addresses how nonuniform fluid shear stress controls the formation of thrombus/neointima and smooth muscle cell migration.

During the early 1980s, the capillary blood vessel networks of the human body were just being understood as dynamic entities, in which the process of angiogenesis could produce dramatic new growth to accomplish wound repair, fracture healing, and help heal the injured heart, as well as produce dangerous growth of tumors by providing them with nutrients. Other vessels, such as larger arterioles and venules, were viewed as much more passive, although there was historical evidence that they could be just as dynamic, adjusting to both biochemical stimuli as well as mechanical stresses. Dr. Fung illuminated the path for many in this field to define the quantitative ways in which physical forces affect blood vessel remodeling, both in the large vessels as well as in the microcirculation. In microcirculation, the complex network architecture and low Reynolds number flow regime combine to produce a system in which knowledge of both individual vessel constitutive properties and the vessel connectivity to other parts of the network are essential to understanding adaptive remodeling. Dr. Fung was the first to realize this and shed light on the problem in the pulmonary circulation. Others then followed the path with analyses of various tissue microcirculations, expanding our understanding of organ capacity for growth and change, and opening the way to today's 21st century designs for engineered tissues with synthetic microcirculatory networks.

It has been shown that cylindrical arteries buckle under hypertensive pressures or reduced axial tension and become tortuous. Arteries often demonstrate geometric variations such as elliptic cross sections and tapering along the longitudinal axis but the effects of these variations on the buckling behavior of the arterial walls have not been investigated. The objective of this study was to determine the buckling pressure and deformation patterns of elliptic and tapered arteries. Models of cylindrical arteries with circular and elliptic cross sections, and circular tapered arteries were generated with the walls modeled as a homogenous isotropic nonlinear material. The buckling analysis of these arteries under lumen pressure was implemented using finite elemental analysis. Our results demonstrated that arteries buckle into tortuous shapes under internal pressure. Oval initial cross sections increased the critical pressure and arteries tend to buckle in the short axis direction. In contrast, tapering reduced the critical buckling pressure and led to skewing of the deformation profile towards the distal end of the artery. The post-buckling behavior of the arteries showed kinking towards the distal end. We concluded that oval arteries are more stable than the circular arteries while tapered arteries are more prone to buckling and kinking with a more tortuous shape in the distal portion. These results will help us better understand the development of vessel tortuosity, such as aorta tortuosity in the abdominal region.

The link between mechanical stimuli and alterations in cellular gene/protein expression is defined by the processes of mechanotransduction. Several cell types, which include osteoblasts, fibroblasts, smooth, cardiac, and skeletal muscle cells, belong to the “mechanocyte” family. These cells are able to detect mechanical signals and transform them into a biological response. Mechanical loads applied to cardiac cells can promote cellular growth (hypertrophy) or degeneration (atrophy). The mechanisms by which cardiac myocytes sense mechanical signals are still being uncovered – structures such as the cell membrane and the internal cytoskeleton and sarcomeres may be involved with stress sensing and mechanotransduction. Recent work has implicated the sarcomeric elastic protein titin and several binding partners in stress-sensing pathways. Defects in mechanotransductive processes may be an independent risk factor underlying cardiovascular maladies including cardiomyopathy and heart failure.

This study is to extract hemodynamic information from echocardiogram to complement the left ventricle ejection fraction (EF) for cardiac evaluation and diagnosis. The data of velocity vector imaging stored in echocardiogram can be used in a novel fluid mechanics analysis for quantification of left ventricular (LV) function. The study is focused on assessing the LV contraction, and is patient specific. Cardiac patients with the same EF could have different LV contraction, which can be identified by the kinetic energy delivered from the wall to blood flow. Both the normal and abnormal wall contraction can be also evaluated by the work done by pressure and shear stresses during systole. The abnormal ventricular contractility can be further assessed by an index for normal velocity effect and by another index for dys-synchrony.

Effects of aging on mechanical properties of human lung are studied. Finite element modeling of human lung tissue under both equi-biaxial and three dimensional (uniform) loading is performed. Experimental results are utilized in building both two and three dimensional models in ABAQUS 6.5 for three age groups: 20, 40 and 60 years old. A computed tomography image of a human lung is simplified to build a three dimensional model. Material properties are defined using linear incremental elasticity. Lagrangian stress-strain relationship is estimated for under various loading conditions in all three age groups. Lagrangian Von-Mises stress trends and values analyzed in the equi-biaxial model appear to be in agreement with biaxial experiments performed by Fung et al. and by Gao et al. This validates that parenchyma can be considered as the main source of lung mechanical properties. Effect of aging on lung stress-strain relationship was similar in both two and three dimensional models. For similar stretch ratios, older age samples are experiencing higher stress values as compared to the younger age samples. This study indicates that finite element simulation utilizing experimental results may be a viable approach to build a virtual testing platform in forecasting the change of lung elasticity with aging at different loading conditions and stretch ratios.

After a review on the modeling of oxygen uptake in pulmonary alveolar capillaries, a summary of our modeling studies developed to represent the sheet flow characteristics of pulmonary capillaries is presented. With the model, we determined the overall pulmonary diffusing capacity D_L, and the diffusing capacities D_M and D_E of the alveolar membrane and the red blood cell (RBC) segments of the diffusional pathway for O₂. Results showed the membrane segment contributing the major resistance, with RBC segment resistance increases as oxygen saturation rises during the RBCs transit: RBC contributed 7% of the total resistance at the capillary inlet (S_O2 = 75%) and 30% towards the capillary end (S_O2 = 95%). Both D_M and D_L increased as the hematocrit increased but began approaching a plateau near a Hct of 35%, due to competition between RBCs for oxygen influx. Both D_M and D_L were found to be relatively insensitive (2∼4%) to changes in plasma protein concentration (28∼45%). The model correlated reasonably with experimental data and can better represent the oxygen uptake of the pulmonary capillary bed.

Dr. Fung has made important contributions to our understanding of the mammalian pulmonary circulation particularly on the sheet-flow concept, distensibility of small pulmonary blood vessels, and fluid dynamics in zone II of the lung. Recently we have become interested in the avian pulmonary circulation where the physiology is very different from the mammalian counterpart, and a comparison of the two is rewarding. In contrast to the situation in mammals, the pulmonary capillaries of birds show extraordinary rigidity in spite of large changes in capillary transmural pressure. The explanation is the support that the blood capillaries receive from the surrounding air capillaries. The epithelial bridges that are attached to the outside of the blood capillaries are able to support a substantial load in spite of being exceptionally thin. The avian pulmonary circulation also shows zone II behavior under some conditions. This is surprising because the sluice-like behavior in zone II is traditionally ascribed to narrowing of the capillary bed, and this does not occur in birds. Possibly the flow characteristics are caused by compression of small veins, and indeed this may be the case in the mammalian lung as well.

In vitro bone cell networks with controlled pattern and intercellular gap junctions were successfully established by using microcontact printing and self assembled monolayers technologies. The intracellular calcium responses of bone cell networks exposed to a steady fluid flow and the underlying signaling pathways were further investigated. The cell network samples were separated into eight groups for treatment with specific pharmacological agents that inhibit pathways significant in bone cell calcium signaling. The calcium transients of the network were recorded and quantitatively evaluated with a set of network parameters. The results showed that gap junction blocker, extracellular ATP pathway inhibitor, and thapsigargin (depleting intracellular calcium stores) significantly reduced the occurrence of multiple calcium peaks, which were visually obvious in the untreated group. The number of responsive peaks also decreased slightly yet significantly when either the COX-2/PGE₂ or the NOS/nitric oxide pathway was disrupted. In the absence of calcium in the culture medium, the intracellular calcium concentration decreased slowly with fluid flow without any calcium transients observed. These findings have identified important factors in the flow mediated calcium signaling of bone cells within an in vitro network.

Spanning a period of a few decades, there have been several models proposed for the elasticity or viscoelasticity of the cytoskeleton. In addition, there have been numerous experiments using cells and reconstituted actin gels, with or without cross-linkers, designed to characterize the rheology of actin networks under various conditions. Still, debates continue regarding the contributions of various potential mechanisms (filament bending stiffness, thermal fluctuations, filament extensional stiffness, cross-linker stiffness, cross-link binding and unbinding) to cell viscoelasticity, and which model (semiflexible polymer network, tensegrity network, cellular solids) is best able to capture the measured characteristics. Here, we use a computational model of a thermally-active cross-linked network to probe the important factors and discuss these in the context of the different models. We conclude that thermal fluctuations are not important in the cytoskeleton, in contrast to the semiflexible polymer network theory. However, both the cellular solids and tensegrity models fail to capture some of the salient mechanical features. For cross-linked networks under prestress, the tensegrity model appears to be the most consistent with the results of our simulations. However, currently no single model satisfactorily captures viscoelastic behaviors of actin networks over a wide range of conditions. Our simulation scheme provides a basis for delineating multiple mechanisms involved in this complex system.

Y. C. Fung introduced me to the biomechanics field in 1979. He advised my Ph.D. research in lung biomechanics (pulmonary blood flow) in 1992, and led me to biomechanics of hearing in 1999. During the past 30 years, I developed my research career in biomechanics based on Fung's mentoring. In this paper, I wish to convey my deep appreciation for his guidance and to recognize his influence in my career, which has taken me to my current research in hearing, both theoretical modeling and experimental measurements of sound transmission through the ear.

The diffusion-induced concentration of various molecules (chemo/cytokines or food/oxygen) around a spherical cell is studied based on an exact mathematical evaluation, arriving at closed-form solutions for a cell with various spatial and temporal distributions of secretion or absorption patterns. In addition, a general method for numerical solution and analytical approximation of such phenomena is presented. The asymptotic behavior of the solution is also examined for long times or great distances from the cell. These can be used to estimate the effective communication parameters among cells. Two examples are used to illustrate the application of the model results under physiologically realistic conditions.

Professor Yuan-Cheng Fung's pioneering work provides a foundation for our understanding of cellular mechanics. Early studies in cellular biomechanics include extensive study of differentiated vascular cells. The more recent proposal to use stem cells for regenerative medicine has prompted study of the role of biomechanics on stem cells. In this brief chapter, we report on work in the Nerem Laboratory evaluating the effects of physiologically-relevant applied physical forces on embryonic stem cells and bone marrow-derived mesenchymal stem cells for vascular applications. Embryonic stem cell-derived endothelial cells (ESC-ECs) respond to applied fluid shear stress similar to vascular endothelial cells. During early differentiation of ESC-ECs, application of fluid shear stress promotes an endothelial phenotype. Mesenchymal stem cells (MSCs), a potential smooth muscle cell-substitute, respond to equibiaxial cyclic strain with cellular rearrangements in a substrate-dependent manner. Gene expression comparison of MSCs with aortic smooth muscle cells reveals that the two cell types have different initial cell signaling profiles and unique responses to applied strain. Taken together, these results demonstrate that the application of physical forces to stem cells can be used to promote differentiation, assess cell phenotype, and discriminate between cell types. Professor Fung's legacy has thus impacted the field of stem cell biology and regenerative medicine.

Often, it can be a chance encounter, a seemingly insignificant conversation, a word of encouragement, or a simple gesture from a respected person that has a tremendous impact on another person's life; and this impact can then be amplified through a series of circumstances, dedicated work, and an inspired passion so as to yield an impact on many, many people that could not have been predicted at the onset. Such was the case when Professor Y.C. Fung visited Taiyuan University at the invitation of Dr. Yang, its president, in 1995 just prior to the 4th China-Japan-US-Singapore Conference on Biomechanics. During that visit, Professor Fung went to the laboratory of Mr. Jin Suo and spent perhaps 10-15 minutes with him, discussing experimental fluid dynamics. This encounter, and subsequent events, changed the career path of Mr. Suo and had an impact on our understanding of hemodynamics and atherosclerosis…

Multi-patient fluid-structure interaction (FSI) studies based on serial magnetic resonance imaging (MRI) data were conducted to quantify correlations between plaque progression and both plaque wall stress (PWS) and flow maximum shear stress (FMSS) and introduce plaque growth functions to predict progression. In vivo serial MRI carotid data from 6 patients (all male; age: 59-73, mean: 67. 3-4 scans/patient; scan time interval: 18 months) were acquired for this study. For each artery, wall thickness (WT), PWS, and FMSS data from 700-900 matched lumen points (100 points per matched slice) were collected for analysis. Point-wise progression was expressed by increase in wall thickness (WTI) at each lumen point. Six growth functions with different combinations of WT, PWS, plaque wall strain (PWSN) and FMSS terms were introduced to predict WT using data from previous scans. 12 cases (out of 15 time-pairs) showed negative correlation between WTI and PWS at current time. FMSS (at current time) showed positive correlation (10 out of 15) with WTI. The growth function including all WT, PWS, PWSN and FMSS factors provided best fit for progression prediction, compared to other 5 growth functions containing fewer factors. More longitudinal case studies are needed before a clinical application can be devised.

Intradialytic hypotension is one of the most adverse effects of hemodialysis. It has been postulated that the cause of hypotension is hypovolemia as more fluid is extracted by the dialyzer than the fluid restituted from the tissue. Many maneuvers have been developed to counter intradialytic hypotension under the premise of hypovolemia. However, there are indications suggesting intradialytic hypotension is due primarily to pooling of blood to abdominal organs. This new hypothesis calls for a new approach to develop effective countermeasures for intradialytic hypotension. After the review of the methodologies to assess hypovolemia and microvascular pooling, countermeasures for intradialytic hypotension, and the use of anti-pooling effect to counter the development of hypotension; we conclude with the recommendation to develop: (1) a monitoring system capable of identifying the responsible mechanisms, (2) a device and/or drug therapy that can counter the effect of blood pooling and/or hypovolemia, (3) the integration of these two for the delivery of personalized countermeasure, and (4) a hemodialysis process that does not induce pooling of blood to abdominal organs for the avoidance of intradialytic hypotension.

This article summarized some of our recently published works on the effects of epidermal pressure on skin flowmotion and discussed the implications to the development of pressure ulcer. Studies were conducted in 5 normal subjects and 5 persons with spinal cord injury (SCI). A series of animal studies were conducted using an established rat model. In the human subject study, external pressure of 16.0kPa was applied to the ischial tuberosity for 30 minutes. In anaesthetized rats, external pressure of 13.3kPa was applied to the trochanter area for 6 hours/day for 4 consecutive days. The normalized amplitude of the metabolic component (0.01-0.02 Hz) and neurogenic component (0.02-0.06 Hz) for persons with SCI was found to be significantly lower during the resting (F=5.26, p=0.032) and post loading conditions (F=5.44, p=0.029) respectively as compared with normal individuals. In anaesthetized rats, prolonged tissue compression induced significant decrease in the normalized amplitude in the frequency interval of 0.01-0.05 Hz in the trochanter area (p<0.001). These findings suggest that the contributions of endothelial related metabolic and neurogenic activities to the blood perfusion regulation became relatively less for persons with SCI during the resting and post loading periods respectively. Also prolonged compression might induce endothelial damage and affect the endothelial related metabolic activities.

In a recently completed large cohort study, this laboratory has identified a significant presence of real-time microvascular abnormalities (vasculopathy) in type-1 diabetes mellitus (T1DM) patients [1, 2]. In addition, a significant correlation between the severity of the vasculopathy with elevated levels of endothelial dysfunction/inflammation biomarkers in the same patients has also been established [1, 2]. Though it is an accepted concept that endothelial dysfunction is normally caused by changes in intraluminal vessel wall shear stress [3-5], the exact pathogenetic mechanism has not been identified. Based on preliminary studies in this laboratory, a mechanism for the pathogenesis of endothelial dysfunction (which could eventually lead to microvascular changes in T1DM) was proposed. We hypothesized that abnormalities in whole blood viscosity (WBV), an important hemorheologic parameter involved in changes in intraluminal vessel wall shear stress, would be significantly elevated in T1DM and should correlate with real-time in vivo microvascular changes in T1DM patients. To test this hypothesis, we have randomly measured WBV in T1DM patients (n=10) to correlate with real-time microvascular abnormalities in the same patients. Using the Rheolog^™, WBV in T1DM patients (n=10) and healthy non-diabetic control subjects (n=10) was measured at a shear rate of 300s^-1. The presence of microvascular abnormalities in the same patients and control subjects was analyzed using the real-time videotape sequences on the conjunctival microcirculation obtained non-invasively via intravital microscopy. A Severity Index (SI), scale 1-15, was computed to reflect degree/severity of vasculopathy in the analysis. T1DM patients compared to control subjects had significantly higher WBV (4.0±0.3cp vs 3.3±0.1cp; P<0.05) and SI (7.1±1.8 vs 0.6±0.7; P<0.05). The results strongly support the independent work from the laboratories of Chien and Garcia-Cardena/Grimbone that the biomechanical forces of blood flow – in particular intra-luminal vessel wall shear stress – play a critical role in regulating endothelial cell function and causing endothelial dysfunction and related microvascular complications [3-5]. It is likely that the biomechanical forces of blood flow play a regulatory role in the homeostasis of the endothelial lining. Therefore, the abnormalities in hemorheologic parameters and realtime microvascular abnormalities (vasculopathic characteristics) identified in the microcirculation in T1DM patients may have cascading effects and thereby contribute to the further worsening of endothelial dysfunction, inflammation and microvascular injury.

Professor Y.C. Fung has made tremendous impacts on humanity through his research and its applications, by setting the highest standards of rigor, via the work of his many students and their students, and due to his exemplary leadership. He has applied his profound knowledge and elegant analytical methods to the study of biomedical problems with rigor and excellence. He established the foundations of biomechanics in a variety of living tissues, including the lung, the heart, blood vessels, blood cells, ureter, intestine, skin, as well as other organs and tissues. Through his vision of the power of “making models” to explain and predict biological phenomena, Dr. Fung opened up new horizons for bioengineering, from organs-systems to molecules-genes, and has provided the cornerstones of research activities in many institutions in the United States and the whole world. He has made superb contributions to education in bioengineering, as well as service to the professional organizations and translation to industry and clinical medicine. He is widely recognized as the Father of Biomechanics and the leading Bioengineer in the world. His extraordinary accomplishments and commands in science, engineering and the arts make him a Renaissance Man whom the world is very fortunate to have.

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In 2007 Professor Satya Atluri and I discussed how to honor Professor and Mrs. Fung on Professor Fung's 90^th birthday. We decided to publish a special series in the Journal of Molecular & Cellular Biomechanics (MCB) in Professor Fung's honor and bind the papers of the special series into a book, entitled “Molecular & Cellular Biomechanics”. This is a very natural thing for MCB to do as Professor Fung is its Honorary Editor. He helped found the Journal and guided its growth.

In addition, we would hold a symposium entitled “Genomic Biomechanics – Frontiers in Biomechanics of 21^st Century” on September 14, 2009 in Professor Fung's honor and make the day a day of festivities paying tribute to the happy couple, Professor and Mrs. Fung, for their more than sixty years of togetherness.

We are heartened that many world leaders in science and engineering, many of whom are friends and colleagues of Professor Fung, lined up to contribute to this special series. There are seven issues with 35 papers covering a wide range of topics in biomechanics spanning from genes, proteins, tissues, organs to human. The first copy of the book, signed by all participants of the symposium and the festive activities, was presented to Professor Fung. Figures 2 and 3 are the covers of the first special issue and the book, respectively.

Thanks to Professors Satya Atluri, Geert Schmid-Schonbein, Shu Chien, Savio Woo, and Peter Chen for organizing the symposium and putting the festive activities together. Also many thanks to all participants of the symposium and the festivities.

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Dr. Fung is the Father of Biomechanics and is referred to as a Renaissance man by several authors in this tribute volume. He has set high standards for himself and others to follow and he has inspired, influenced and affected the lives of many who crossed his path…

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Please refer to full text.

We celebrate the 90^th Birthday of one of the giants of our time. The grand vision of Professor Y.C. Fung, often called the “Father of Biomechanics”, has become a reality. Mechanics and Biology have started to fully embrace and a new generation of bioengineers is starting to emerge that has never known engineering other than being based on a merger of four basic sciences: biology, chemistry, physics and mathematics. We owe a great dept to Professor Fung, congratulate him for such a vision, and thank him for decades of inspiration and warm friendship.

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Professor Yuan-Cheng Fung is a leading scientist in the field of bioengineering. His devoted research in this field covers the span of over four decades. His vision is to understand the world and life; his mission is to make contributions in the advancement of science; his passion is the ongoing quest of knowledge and the discovery of truth. Norman Cousins once described Dr. Jonas Salk, the famous developer of the polio vaccine, “You represent the perfect marriage of science and art as it is and as it should be.” Professor Fung is a member of the National Academy of Sciences, National Academy of Engineering and Institute of Medicine. He received the National Medal of Science in 2001.

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It is with great pleasure that I reflect on Prof. YC Fung's 90^th Birthday. I was very fortunate to be one of his last students. I recall the journey vividly and especially my first encounter. I was a junior undergraduate majoring in Chemical Engineering when I noticed a possible technical elective called “Biomechanics”. I knew little of the subject but only that “Bio” was life and “Mechanics” was a branch of physics that dealt with motion and forces that caused them. This course was taught by YC Fung, part of a curriculum he had established at UCSD. I recall he came to class empty handed but before the lecture was over, the board was filled with well proportioned conceptual drawings (he is an artist) of function of organs (he is a physiologist) with equations that described the concepts (he is a mathematician) and many deep insights that revealed the essence of the problem (he is a poet). But actually he is a bioengineer; one of the many terms he coined in the field he seeded and nurtured (Kassab, 2004)…

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When I finally decided to move from the University of Maryland at Baltimore to the University of California, San Diego (UCSD) in 1998, I wrote a letter to Dr. Fung, a pioneer in studies on pressure, flow, stress and remodeling of the pulmonary vasculature. I did not expect to receive any response, but got a warm welcome letter from Dr. Fung within a week. Right after my arrival at UCSD in 1999, I had an opportunity to have lunch with Dr. Fung in the Faculty Club during which we talked about science, life, and the future direction in the research field of pulmonary vascular pathophysiology. Although I have never worked directly with Dr. Fung, I feel, since that lunch, I have learned a lot from him, probably even more than many of his graduate students and postdoctoral fellows. His smile, his patience, his, sometimes, loud laughter, his positive attitude about life, his passion about science and research, his knowledge about history and culture, his generosity, his willingness to spend time with those who need his guidance …My wife and I have asked ourselves many times, how come an eminent scientist and internationally recognized pioneer can still be so nice, approachable, and sensible. Dr. Fung is not only a role model for us in research and science, but also a guide for us to have an enjoyable and meaningful life…

John Guare's play, “Six Degrees of Separation” refers to the connectivity of the human web on planet Earth. The theory states that if our opinions and influences reach every individual we know, then reach every individual they know, and so on, six times, our influence would reach everyone on the planet. However, in the biomechanical world, thousands of students, professors, engineers, and scientists around the globe are separated by a mere three degrees or less from the pioneering work of Prof. YC Fung. The three degrees can simply be stated as: those who used Prof. Fung's research and findings in their work, those who have been trained by Dr. Fung's students, and those who have had the privilege to study directly under him: at the center of biomechanics stands Prof. Fung himself. I am among the lucky few who can claim to have touched the center of the biomechanical world and it has left a lasting impression on my work and my life…

To understand our father's inner harmony and how he could achieve so much with such apparent ease, we cite one of his favorite sayings, “Easy to Do, Hard to Know,” as a unifying theme for his life as a model of Choice coupled with Commitment.