Cell Shape: Regulating Forces & Mechanics

Cell shape is the product of the balance between biochemical and mechanical signaling. A wide variety of fundamental physiological processes (division, migration, development, etc…) rely on the cell being able to either maintain its shape, or alter it in a tightly regulated manner. Cells accomplish these feats by coordinating in both space and time the thousands of simultaneous molecular interactions which determine the local material properties of the cell. While these individual molecular interactions have been studied in great detail, we lack an understanding of how the cell coordinates these interactions at the cellular and tissue length scales. Put more simply: how does the cell know where and how hard to pull? And how does the cell know to resist deformation or undergo a shape change? To tackle these questions we use a combination of techniques, including Traction Force Microscopy (TFM), micropatterning, computational modeling, and genetic, optogenetic and pharmacological perturbations.

Mechanosensing

Non-biochemical signals from the surrounding external environment, such as ligand density and distribution, fluid shear stress and environmental stiffness, play an equally important role in regulating cell shape and cytoskeletal architecture. In particular, the stiffness of the Extracellular Matrix (ECM) has been shown to directly influence signaling, differentiation, metastasis and even cell spreading. Despite this behavior appearing to affect a wide variety of cell types and processes, we currently do not understand how cells translate physical signals into biochemical ones. The lab is focused on trying to understand how adhesions and the cytoskeleton might play a role in cells interpreting mechanical signals from the extracellular environment. To this end we use polyacrylamide substrates, whose Young's moduli can be controlled easily, to explore the role of stiffness in processes like cell spreading and migration.

Cytoskeletal Architecture & Dynamics

The cytoskeleton is a continually self-organizing and rearranging network of filamentous proteins that control the cell's local mechanical properties and determine its shape. In conjunction with their associated cross-linkers, motors and regulatory binding proteins, these filaments form specific architectures that are spatially and temporally regulated by the cell to facilitate different processes in the cell. In the lab we are specifically focused on two of these filamentous proteins, actin and septin, and their roles in coordinating cellular adhesion, migration and force generation. We use high resolution imaging in combination with novel image processing techniques to identify and quantify filament organization in cells and purified protein systems.