Physical Society Colloquium

The Phases and dephases of cellular architecture

Stephen Michnick

Département de Biochimie
Université de Montréal

Over a century ago a popular theory about the organization of matter in living cells emerged from early microscopic observations of living cells. This theory posited the cell to be divided into a number of unique phase-separated bodies composed of living matter. This “protoplasmic” theory of the cell survived into the 1920's forming the central theme of a theory of the origins of life, proposed by the Soviet biochemist Alexander Oparin. In the ensuing century, these ideas were somehow lost in the clamor towards reductionist molecular and structural biology. Recent years have seen emerge renewed interest in these ideas and compelling evidence that biopolymers can phase separate into viscoelastic bodies serving as isolated reaction vessels or storage granules for different substances. We are exploring the idea that another potential function of such liquid-liquid phase separation (LLPS) of biopolymers could be involved in generating forces that drive the organization of matter and cellular morphogenesis. In this talk I will first review some of the history and recent discoveries concerning LLPS. I will then turn to our own studies on a major mechanism of uptake and control of the composition of cellular membranes called clathrin-mediated endocytosis (CME). I will describe evidence that the energy required for the early stages of CME is mediated by liquid-liquid phase separation from the cytoplasm of proteins with low complexity amino acid sequences. The work required to drive the generation of membrane vesicles (endosomes) is due to adhesion, dominating over interfacial tensions among the droplet, cytosol and membrane. I will illustrate how a combination of biophysics and bioinformatics approaches revealed this model and could be used to predict other forms of large-scale organization of matter in living cells, how these organizations may determine cellular architecture and their dynamics, such as organizing the genome and how they may partition distinct, but complementary biochemical process. Finally, I will reflect on how material properties of cells, particularly as they age, may contribute to human disease pathogenesis, notably to the origins of several neurodegenerative diseases.

Biography:
Stephen Michnick did his bachelor and doctoral studies in Physics at the University of Toronto under the direction of Jeremy Carver; and his postdoctoral training in the Department of Chemistry and Chemical Biology at Harvard University, with Profs. Martin Karplus and Stuart Schreiber. He studied structures of carbohydrate-protein and protein-protein complexes, as well as mechanisms of protein folding and protein chemistry. At the heart of his work, protein chemistry remains central; his fundamental research program leverages new technologies to investigate the fascinating organization and dynamics of biochemical networks in living cells and how these networks compute cell-fate decisions. He enjoys speaking with students and you will have fun at the talk.