How Mechanical Signals Regulate Biological Function

Mechanical interactions are vital components of the most fundamental cellular processes. Without them, cells would be unable to divide, change shape, move or even form multicellular tissues. Using a process called mechanotransduction, cells can convert these mechanical signals into biochemical signals to regulate their behavior. These mechanical interactions can happen both inside of the cell and between the cell and its extracellular environment. In either case, cells must spatially and temporally control both the magnitude and kinetics of these interactions. Our lab is interested in how cells generate, interpret, and use mechanical signals to regulate their behavior. We combine traditional biological approaches with a number of quantitative approaches, including high-resolution microscopy, micropatterning, computational modeling and optogenetics.

Current Projects

Mechanobiology of Septin Filaments

The cytoskeleton is a network of filamentous proteins that is continually self-organizing and rearranging in response to different stimuli. In conjunction with various cross-linkers, motors and regulatory binding proteins, these filaments form specific architectures that spatially and temporally regulate many mechanical interactions in the cell. While the cytoskeleton's two most famous components, actin and microtubules, have been studied in great detail, significantly less is known about septins. Septins localize to many mechanically active regions such as the cleavage furrow and the base of cilia, and recognize specific regions of curvature in the membrane. We are interested in potential roles septins might play in organizing and transmitting forces in the cytoskeleton and any mechanosensitive properties they might display.

Mechanosensing via LIM domain proteins

While cells are clearly sensitive to mechanical signals, the mechanisms that mediate this behavior remain unclear. We are approaching this topic from two angles. First, at the protein scale, a number of members in the LIM family, including the focal adhesion proteins zyxin and paxillin, have been shown to be mechanosensitive. Previous research has identified that the LIM domains are sufficient to localize to regions of strain in the cytoskeleton. We are thus interested in how LIM domain proteins recognize strain and whether these mechanisms are conserved across all LIM containing proteins. Second, at the cellular scale, we are interested in how mechanosensitive behaviors emerge from the network activity of the entire cytoskeleton and its components. Specifically we are interested in the basic questions of how cells know where and how hard to pull on their extracellular environment.

Mechanics of Amoeboid Migration

Cell migration is classically understood through the cyclical repetition of the mechanical processes of protrusion, contraction, and retraction. This cycle accurately describes the slow, steady migration that depends on discrete adhesion sites and contractile bundles that characterize almost all mesenchymal cells. Amoeboid migration on the other hand, is characterized by the lack of distinct and discrete adhesion sites and is thought to be powered via polymerization dynamics of branched actin networks. This migration mode is most often associated with immune cells, but is also accessible by mesenchymal cells in low adhesive and confined environments. We are interested in understanding how cells interact physically with the extracellular environment when they utilize this alternative migration mode.