NSF-ANR: Co-Dynamics of Contraction and Adhesion in Animal Morphogenesis

University Of Chicago, Chicago IL

Investigators

Abstract

A central challenge in biology is to understand how groups of cells rapidly and collectively deform themselves during early development. Actomyosin-based contractile networks produce the forces that deform cells, while adhesion networks transmit those forces across cell-cell contacts. These networks must continuously remodel themselves as cells move, divide and exchange neighbors. But how they do so, and how each shapes the organization and dynamics of the other, remains poorly understood. We will address this challenge in nematode worm embryos, combining advanced microscopy, genetic and biophysical manipulations and mathematical modeling. In addition to providing new insight into mechanisms that govern the rapid remodeling of early embryos. The project will provide students with valuable cross-training at boundaries of biology, physics and mathematics. The PI will incorporate concepts and methods emerging from this work into undergraduate and graduate level courses in biological dynamics, and into a new practical course in microscopy to be taught at the MBL. The goal of this multidisciplinary collaborative effort is to understand how the macroscopic dynamics of force transmission emerge from the microscopic dynamics and coupling of contractile and adhesion networks in early C. elegans embryos. We will leverage cutting edge microscopy tools to characterize the microscopic dynamics of adhesion network assembly and remodeling as new contacts form and grow. We will determine how the architecture of adhesion networks are shaped by actin network architecture, contractility and flow, and how in turn, patterns of contractility and flow are shaped by anchorage of contractile networks at cell-cell contacts. Finally, we will use physical theory and modeling, constrained by microscopic observations and biophysical measurements, to understand how physical coupling between these two networks controls the balance of frictional slippage and force transmission across contacts. This work will yield fundamental new insights into how early embryos can orchestrate rapid remodeling using the highly conserved molecular machinery that governs contractility and adhesion. It will provide a unique interdisciplinary training opportunity for both graduate and undergraduate students, and the conceptual and methodological results from this work will inform the development of new lectures and course modules for two quantitative biology courses and a new hands-on microscopy course taught by the PI. This collaborative US/France project is supported by the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.