Single-Cell Biophysics: Measurement, Modulation, and Modeling

Single-Cell Biophysics: Measurement, Modulation, and Modeling

Tuesday Speaker Abstracts

Local 3D Single-Cell–Matrix Interactions Underlie the Spatiotemporal Dynamics of Cell Populations Nicholas Kurniawan . Eindhoven University of Technology, Eindhoven, Netherlands. It is increasingly accepted that the physical and mechanical properties of the extracellular environment play a guiding role in cell behavior, for instance during development, wound healing, and cancer metastasis. Cells sense physical and mechanical cues from the extracellular matrix (ECM) and transduce these cues into intracellular signals that can, in turn, affect cell response. However, surprisingly little is known about what the cells are actually sensing, especially in the context of the typically complex, nonlinear, and fibrillar ECM. We hypothesized that cells sense the local, rather than global, ECM properties, and base their decision-making on such local mechanosensing. To test this hypothesis, we developed a spatially-resolved microrheological technique that provides quantitative information about the local viscoelasticity around single cells at sub- cellular resolution. We seeded cells in 3D collagen gels and found that cells created pockets of stiffened microenvironment, suggesting that cells ‘prime’ their surrounding ECM to support contractility. To determine whether cells rely on local mechanosensing for decision-making, we systematically modulated the ultrastructure of fibrin fibers, allowing us to independently vary the stiffness at network and fiber levels. We show that cell spreading and differentiation are determined by the stiffness of individual fibers, rather than by the bulk properties of the matrix. These two findings strongly suggest that the cell and the matrix can locally influence and adapt to each other in a reciprocal manner. We further speculated that such local and dynamic cell– matrix interactions may manifest in a heterogeneity of cell phenotype within a population. Indeed, we found a spatiotemporally-heterogeneous pattern of cell migration in 3D collagen gels that is mediated by cell-induced local ECM remodeling. These results reveal the role of cell– matrix interactions in single cell behavior and population dynamics.

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