Physical Society Colloquium

Using single-molecule biophysics to understand the physical basis of multicellularity

Alex Dunn

Department of Chemical Engineering
Stanford University

Multicellular life reflects the ability of hundreds to millions of living cells to assemble into three-dimensional tissues. This assembly process is mediated by protein structures termed adhesion complexes, which link cells to each other and to the extracellular matrix (ECM). Understanding how multicellular tissues form presents a hierarchy problem, in which subtle changes to individual adhesion proteins (nm) can radically alter the structure and function of tissues or even whole organisms (mm-m). In this talk I discuss what we have learned about how the collective properties of multicellular tissues may arise from the molecular-scale properties of individual adhesion complexes. In the first half of the talk I describe a single-molecule, optical-trap based assay that has allowed us to reconstitute the essential components of the cadherin-based protein complexes that link neighboring cells. The second half of the presentation describes our use of fluorescent molecular force sensors to elucidate the essential physical properties of the protein assemblies that link cells to the ECM. Both classes of measurement support an emerging understanding in which adhesion complexes act as sophisticated sensors that actively respond to mechanical inputs, both to maintain tissue integrity and to drive the complex cellular rearrangements that underlie embryonic development.