Oct. 15 - Amrinder S. Nain, Ph.D.
Fiber Curvature Drives Cell Protrusive Behavior
Amrinder S. Nain, Ph.D.
Associate Professor of Mechanical Engineering, Virginia Tech
Native fibrous proteins of small to large diameters (tens of nm to microns) distributed in various configurations (sparse/dense or random/aligned) form the complex and heterogeneous fibrous extracellular microenvironment (ECM). Cells probe and navigate the ECM through the formation of force exerting protrusions of varying morphologies. Despite decades of in vitro studies, our knowledge of fiber curvature driven cell protrusive behavior remains in infancy. In this talk, I will discuss our approach of using suspended fibers of controlled diameters (large: 2000 nm to small: 100 nm) mimicking the native ECM dimensions for studying single protrusions in-line with and lateral to cell-body migration direction. First, using aligned parallel fiber networks that also act as force sensors, I will discuss our findings in force driven (i) spatiotemporal distribution of focal adhesions and cytoskeleton-nucleus caging during anisotropic cell stretching, and (ii) utility of lateral and suspended twine-bridges in cell spreading. Second, using a network of orthogonal fibers, I will discuss our method of isolating protrusions independent of cell-body migration direction. This approach enables us to develop morphodynamic metrics that quantitatively describe cell-specific protrusive behavior (protrutyping), and we show a diminished role of intermediate filament vimentin in the formation of protrusions of long lengths. Altogether, using ECM-mimicking fiber networks in various configurations, we demonstrate the ability to isolate and interrogate cell protrusive behavior in a controlled and repeatable manner.