Research

Living cells generate mechanical forces to carry out their functions, and most of that force comes from the actin cytoskeleton, a network of protein filaments inside the cell. Myosin motor proteins walk along these filaments, using chemical energy from ATP to pull on them, much as they do in muscle. We study how the properties of individual motors and filaments, and the way they are arranged and constantly rebuilt, add up to the contraction of the whole network. This helps explain how cells pulse, change shape, and break symmetry in order to move or divide.

Depending on conditions, the actin cytoskeleton can behave like an elastic solid or flow like a viscous fluid, and this shapes how cells respond to the forces they experience. Actin filaments are held together by crosslinking proteins that bind, unbind, stretch, and in some cases grip harder when pulled. We investigate how these microscopic connections, along with the breaking and rebuilding of filaments, determine how the network is organized, how stiff it is, and how it relaxes under stress, in settings ranging from purified networks to cells in the eye.

Cells in the body are surrounded by the extracellular matrix (ECM), a soft scaffold made of proteins such as collagen. Forces generated inside a cell are transmitted to this matrix, and cells can deform it and permanently reshape it. Working with experimental collaborators, we model how cells push and pull on their surroundings: how a dividing cell makes room for itself in a crowded space, how the stiffness and structure of the matrix can block or enable invasion by cancer cells, and how groups of cells reorganize the matrix as they move together.

Cell migration underlies wound healing, development, and the spread of cancer. Besides chemical signals, cells can be guided by mechanical cues; many cells, for example, tend to move toward stiffer regions, a behavior called durotaxis. We've developed computational models of cell migration that show how cells sense and follow differences in stiffness, how cells and their surroundings reinforce each other as cells move, and how contact between neighboring cells gives rise to the coordinated movement of whole groups.