Single-molecule mechanical studies of unstable protein building blocks

Abstract: The most abundant protein on earth, collagen, is the material building block that forms the basis of our connective tissues and the extracellular matrix that surrounds our cells. It performs important structural and mechanical roles, holding our bodies together and helping our tissues to withstand a wide variety of forces. Surprisingly, collagen proteins are structurally unstable at body temperature.

In this talk, which will be aimed at a diverse audience, I will introduce some of the fascinating physical properties of the unique triple-helix structure of collagen and will describe tools we are developing to study its nanoscale structural and mechanical properties. These tools combine approaches from physics, chemistry, engineering, computer science and cell biology to provide deep insight into structure-function relationships. In particular, I will focus on our findings using the techniques of atomic force microscopy and centrifuge force microscopy to study these properties, one molecule at a time. Our work is revealing clues as to how stability is encoded within collagen’s sequence, and how collagen’s triple helix balances structural stability with responsiveness to applied force and its chemical and thermal environment.