CAREER: Nonequilibrium organization in epithelial sheets

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

TECHNICAL SUMMARY The Division of Materials Research and the Division of Molecular and Cellular Biosciences contribute funds to this CAREER award. This award supports theoretical research and education that applies ideas from condensed matter physics to understand the organization of active cellular systems, with epithelial sheets in biology serving as a particular inspiration. These quasi-two-dimensional, planar assemblies of mechanically coupled cells are the basic building blocks of most tissues and organs, and their movements and rearrangements are at the root of much of animal morphogenesis. Topics to be studied include the mechanisms that array cells in the sheets in intricate, reproducible patterns and the ways that cells interact to induce large-scale tissue movements. Recent years have seen growing interest in the statistical physics of systems far from thermodynamic equilibrium, also called active systems, including in particular biologically-inspired systems like collections of molecular motors and cytoskeletal filaments. These efforts have lead to a number of theoretical advances, but so far, most work has focused either on systems in an infinite continuous space or on simple geometries meant to mimic the interiors of individual cells. Higher animals and humans, however, are made up of complex tissues consisting of many cells whose mechanical interactions play a central role in regulating myriad biological processes. Despite the fact that each of these cells is a living, active system, models at the tissue scale have with a few exceptions been limited to descriptions based on the equilibrium mechanics of passive solids. With this award, the PI will seek to bridge this gap. Specifically, he will: 1. Study generic instabilities of cells in epithelial sheets, including those tied to cell polarization, which has strong analogies with magnetic ordering in equilibrium systems. 2. Formulate phenomenological models of interacting active cells dictated by symmetries and conservation laws. 3. Construct 'mesoscopic' models of active gels within mechanically coupled cells. These models will open the way to studying recently discovered subcellular organization in epithelia such as traveling waves of actin density that propagate from cell to cell. This research program will lay the groundwork for more detailed studies of specific biological epithelia, including those implicated in human developmental defects, and may provide the inspiration for the construction of active biomimetic systems that can replicate the extraordinary order, control, and accuracy that characterizes their biological inspirations. This award will support the interdisciplinary education of undergraduate and graduate students; the PI will make a concerted effort to recruit members of under-represented minorities to his research group. The award will also support the development of a museum exhibit and a series of public lectures on topics related to the research and the refinement of course materials to support the introduction of peer instruction methods in upper-level physics courses. NON-TECHNICAL SUMMARY The Division of Materials Research and the Division of Molecular and Cellular Biosciences contribute funds to this CAREER award. This award supports theoretical research and education that applies ideas from condensed matter physics to understand the organization of active cellular systems. Physicists have developed a number of powerful theoretical techniques to understand the origins of regular, periodic order in inert, physical systems such as solids or liquids. Similar-seeming order is seen in biological systems, but it is unclear to what extent the same mechanisms drive the organization of living cells which constantly consume energy. The research funded by this award will seek to answer this question for a particular class of biological systems, epithelial sheets. These planar assemblies of mechanically coupled cells are the basic building blocks of most tissues and organs, and their movements and rearrangements are central to the development of adult animals from fertilized eggs. Specifically, the PI will: 1) Classify the instabilities by which groups of cells in epithelial can suddenly rearrange their packing. 2) Understand what physical properties of epithelia are independent of their detailed microscopic organization. 3) Develop theoretical techniques that will connect biochemical and biophysical knowledge about particular cellular components to large-scale organization. This research program will lay the groundwork for more detailed theoretical studies of specific biological epithelia, including those implicated in human developmental defects, and may provide theoretical guidance for the construction of active biomimetic systems that can replicate the extraordinary order, control, and accuracy that characterizes their biological inspirations. This award supports the interdisciplinary education of undergraduate and graduate students; the PI will make a concerted effort to recruit members of under-represented minorities to his research group. It also supports the development of a museum exhibit and a series of public lectures on topics related to the research and the refinement of course materials to support the introduction of peer instruction methods in upper-level physics courses.