Narrow Results

This discussion about diagnostic tests for cancer incorporates a powerful branch of Physics namely X-ray diffraction. Although this technique was used to solve the DNA structure using the X-ray diffraction pictures of Rosalind Franklin,¹ and the structure of vitamin B12 by Dorothy Hodgkin² and hosts of other medical related structures, it is poorly understood by the general medical profession and the community at large. To the nonphysicist the patterns appear to have no relation to the results produced. It might as well be written in Greek. The well-known quote of Poincaré, the famous French mathematician and scientist, in 1885 comes to mind: "Science is built up with facts as a house is with stones. But a collection of facts is no more a science than a heap of stones is a house."

In order therefore to build a true understanding of this powerful technique it is necessary to build a firm understanding of the basic facts about this technique, so that the final results will be clear to all, as they will be held up by a firm house of knowledge. So let us take up the first stone.

Type I collagen fibrils have circular cross sections with radii mostly distributed in between 50 and 100 nm and are characterized by an axial banding pattern with a period of 67 nm. The constituent long molecules of those fibrils, the so-called triple helices, are densely packed but their nature is such that their assembly must conciliate two conflicting requirements. One is a double-twist around the axis of the fibril induced by their chirality and the other is a periodic layered organization, corresponding to the axial banding, built by specific lateral interactions. We examine here how such a conflict could contribute to the control of the radius of a fibril. We develop our analysis with the help of two geometrical archetypes: the Hopf fibration and the algorithm of phyllotaxis. The first one provides an ideal template for a twisted bundle of fibres and the second ensures the best homogeneity and local isotropy possible for a twisted dense packing with circular symmetry. This approach shows that, as the radius of a fibril with constant double-twist increases, the periodic layered organization can not be preserved without moving from planar to helicoidal configurations. Such changes of configurations are indeed made possible by the edge dislocations naturally present in the phyllotactic pattern. The distribution of those defects is such that the lateral growth of a fibril should stay limited in the observed range. Because of our limited knowledge about the elastic constants involved, this purely geometrical development stays at a quite conjectural level.

Tumor invasion, the process by which tumor cells break away from their primary tumor and gain access to vascular systems, is an important step in cancer metastasis. Most current 3D tumor invasion assays consisted of a single tumor cell embedded within an extracellular matrix (ECM). These assays taught us much of what we know today on how key biophysical (e.g., ECM stiffness) and biochemical (e.g., cytokine gradients) parameters within the tumor microenvironment guided and regulated tumor invasion. One limitation of the single tumor cell invasion assays was that it did not account for cell–cell adhesion within the tumor. In this paper, we developed a micrometer scale 3D co-culture spheroid invasion assay that recapitulated physiologically realistic tumor microenvironment and was compatible with microscopic imaging. Micrometer scale co-culture spheroids (1:1 ratio of metastatic breast cancer MDA-MB-231 and non-tumorigenic epithelial MCF-10A cells) were made using an array of microwells, and then were embedded within a collagen matrix in a microfluidic platform. Real time imaging of tumor spheroid invasion revealed that the spatial distribution of the two cell types within the tumor spheroid critically regulated tumor invasion. This work linked tumor architecture with tumor invasion and highlighted the importance of the biophysical cues within the bulk of the tumor in tumor invasion.

Collagen is an endogenous fluorophore that accounts for about 70% of all proteins of human skin, so it can be an optical marker for structural abnormalities in tissues registered by laser fluorescent diagnostics in vivo. Using the examples of such abnormalities as scars, scleroderma and basal cell carcinoma, this study shows the differences between coefficients of fluorescent contrast k_f(λ) of abnormalities from the ones for healthy tissues at fluorescent excitation wavelength 360–380 nm. It is shown that scars and dysplasia are characterized by reduced values of k_f(λ) for collagen. Due to high turbidity and phase heterogeneousness as well as variation of parameters of blood microcirculation and concentrations of other related chromophores, there is no mathematical model that precisely calculates the concentration of collagen in tissues only with the use of the value of fluorescent signal intensity. So, probably, the best marker of the pathological process is a comprehensive representation of k_f(λ) for all endogenous fluorophores, i.e., for all used visible wavelengths. In this case identification of abnormal tissues is quite possible by detecting some deviations of coefficients k_f(λ) for the optically identical and symmetrical regions of the human body.

Changes of the blood vessels and collagen are associated with the development of abnormal cervical cells. Recently, optical coherence tomography and Mueller polarization images were used to provide information regarding the presence of collagen fibers in the cervical tissue. However, most of these methods need a lot of time for image recording and are expensive. In addition, the general survey on the absorption and distribution characteristics of collagen and blood in the cervical is still lacking. In this study, we developed a colposcopy combining cross-polarized image and image processing algorithm with an efficient analytical model to map the distribution of blood and collagen in the uterine. For this system’s proof of concept, we captured and processed the case of cervical ectopy and Nabothian cyst. The results show that the distribution of blood and collagen maps matched with anatomical and physiological when compared with Lugol’s iodine images. This technology has some advantages, such as low cost, real time, and can replace the use of acetic acid or Lugol’s iodine in the future.

Tissue engineering is an innovative field of research applied to treat intestinal diseases. Engineered smooth muscle requires dense smooth muscle tissue and robust vascularization to support contraction. The purpose of this study was to use heparan sulfate (HS) and collagen coatings to increase the attachment of smooth muscle cells (SMCs) to scaffolds and improve their survival after implantation. SMCs grown on biologically coated scaffolds were evaluated for maturity and cell numbers after 2, 4 and 6 weeks in vitro and both 2 and 6 weeks in vivo. Implants were also assessed for vascularization. Collagen-coated scaffolds increased attachment, growth and maturity of SMCs in culture. HS-coated implants increased angiogenesis after 2 weeks, contributing to an increase in SMC survival and growth compared to HS-coated scaffolds grown in vitro. The angiogenic effects of HS may be useful for engineering intestinal smooth muscle.