Building a Proportional Cell: Statistical Physics of Subcellular Size Control

Brandeis University, Waltham MA

Investigators

Abstract

NONTECHNICAL SUMMARY The Division of Materials Research, the Division of Molecular and Cellular Biosciences, and the Physics Division contribute funds to this award. This award supports theoretical research and education on fundamental questions of cell biology with implications for biomaterials and statistical physics. A remarkable feature of all living cells is that they contain many subcellular parts called organelles that perform different functions. Organelles come in different sizes and shapes and these physical attributes are often intimately related to their function. For example, mitochondria are compartments filled with lipid membranes folded upon themselves many times over. The large membrane supports protein machines that are imbedded in the membrane and whose function is to make cellular fuel molecules. Similarly, cells build long polymer cables of length precisely matched to the size of the cell, and are used to transport materials from one side of the cell to the other. These observations motivate the question: How do cells assemble such three-dimensional structures? While genes encoded in the cell's DNA carry the information needed to make the molecular building blocks, how they self-assemble into intricate and functional three-dimensional structures remains largely unknown. The PI will consider these fundamental questions using mathematical models for assembly of subcellular structures. These models will be tested against experimental data obtained by several collaborating biology labs. The goal will be to identify common design principles for assembly that lead to sub-cellular structures of a well-defined size and shape. New experiments in cells will be stimulated leading to potentially useful insights for making synthetic materials which self-assemble into specific shapes and sizes. The interdisciplinary nature of the research will provide opportunities for physics students to engage in cutting edge biological research. It will provide them with skills necessary to be effective members of an interdisciplinary research team consisting of biologists and physicists. These skills are particularly important for the science, technology, engineering and mathematics workforce of the future since most of the big problems facing society will require a concerted effort of scientists from different disciplines. TECHNICAL SUMMARY The Division of Materials Research, the Division of Molecular and Cellular Biosciences, and the Physics Division contribute funds to this award. This award supports theoretical research and education on fundamental questions of cell biology with implications for biomaterials and statistical physics. Subcellular structures in cells have been observed for hundreds of years and yet it is only recently that we have developed the experimental tools to address key questions about them, such as: How do cellular organelles obtain their specific shapes? How do cells control their number and size? How does a cell 'decide' how many mitochondria should it have? How does a cell construct structures with precisely arranged parts, such as sarcomeres in muscle with its regimented arrays of actin filaments interdigitated with myosin fibers? The cytoskeleton provides a particularly fruitful arena in which to develop quantitative models that address these questions of morphology. Namely, over many years biologists have obtained a wealth of quantitative information about the structure and dynamics of the cytoskeleton. This work has produced a parts list of molecules that the cytoskeleton is made of, and how these molecules interact, while the question of how these interactions are coordinated in space and time inside the cell remains largely unanswered. The PI will use theoretical physics and mathematics to develop a common language for describing the various size control mechanisms of cytoskeleton structures. An assembly of sub-cellular structures will be investigated as a stochastic process that involves different molecular components and mathematically different feedback mechanisms that cells employ to control their size will be studied. The proposed research will advance the fields of statistical physics, cell biology, and biomaterials. One of the key features of the proposed theoretical research is a close collaboration with experimental labs that study assembly dynamics of actin structures in yeast, the assembly of cilia in mouse hair cells, and of nucleoli in developing embryos of the worm C.elegans. It will also help train theoretical physicists interested in working on fundamental problems in cell biology.