Effect of Fibrin Glue on the Biomechanical Properties of Human Descemet's Membrane

10.1371/journal.pone.0037456PLoS ONE75

Mechanical adaptability of cell migration in 3D collagen gels

Migration of cells across tissues with diverse biophysical environments plays a crucial role in a wide variety of physiological functions and pathological processes, such as in embryonic development, wound healing, haemostasis, tumor and cancer progression. Indeed, one of the most devastating features of cancer is metastasis_the ability of cancer cells to escape from the primary tumor and invade and colonize a distant tissue. Understanding the biophysical and biochemical mechanisms underlying cell migration remains a challenge, however, partly because it has been only recently realized that cells employ different strategies and molecular mechanisms in three-dimensional (3D) environments, compared to on traditional 2D glass surfaces.\u3cbr/\u3e\u3cbr/\u3eIn this work, we examined cell migration, simultaneously at the individual cell and cell population levels, in a 3D collagen hydrogel model mimicking the connective tissue topology confronted by malignant breast cancer cells. Our findings revealed two distinct migration patterns that depend specifically on the location of the individual cells within the population: a rapid and directionally persistent migration of the “leader cells” and a more randomized migration of the “follower cells”. This disparity, strikingly, occurred with minimal cell-cell contacts. Rather, this heterogeneity is associated with local remodeling of the pericellular matrix and results in an apparent independence of the inherent migration on matrix condition. Despite such robustness, effects of anti-migratory drugs were interestingly observed to vary strongly with matrix stiffness and architecture. Specifically, cytoskeletal contractility-targeting drugs reduced migration speed in sparse gels, whereas migration in dense gels was retarded effectively by inhibiting proteolysis. Our results therefore corroborate a mechanistic plasticity that allows cells to actively adapt their invasion machinery depending on the local biophysical microenvironment.\u3cbr/\u3

Concentric gel system to study the biophysical role of matrix microenvironment on 3D cell migration

The ability of cells to migrate is crucial in a wide variety of cell functions throughout life from embryonic development and wound healing to tumor and cancer metastasis. Despite intense research efforts, the basic biochemical and biophysical principles of cell migration are still not fully understood, especially in the physiologically relevant three-dimensional (3D) microenvironments. Here, we describe an in vitro assay designed to allow quantitative examination of 3D cell migration behaviors. The method exploits the cell’s mechanosensing ability and propensity to migrate into previously unoccupied extracellular matrix (ECM). We use the invasion of highly invasive breast cancer cells, MDA-MB-231, in collagen gels as a model system. The spread of cell population and the migration dynamics of individual cells over weeks of culture can be monitored using live-cell imaging and analyzed to extract spatiotemporally-resolved data. Furthermore, the method is easily adaptable for diverse extracellular matrices, thus offering a simple yet powerful way to investigate the role of biophysical factors in the microenvironment on cell migration

Mechanobiology of cell migration in the context of dynamic two-way cell–matrix interactions

Migration of cells is integral in various physiological processes in all facets of life. These range from embryonic development, morphogenesis, and wound healing, to disease pathology such as cancer metastasis. While cell migratory behavior has been traditionally studied using simple assays on culture dishes, in recent years it has been increasingly realized that the physical, mechanical, and chemical aspects of the matrix are key determinants of the migration mechanism. In this paper, we will describe the mechanobiological changes that accompany the dynamic cell–matrix interactions during cell migration. Furthermore, we will review what is to date known about how these changes feed back to the dynamics and biomechanical properties of the cell and the matrix. Elucidating the role of these intimate cell–matrix interactions will provide not only a better multi-scale understanding of cell motility in its physiological context, but also a more holistic perspective for designing approaches to regulate cell behavior