Evolutionary mechanics of adhesion molecules

F. Rico

(Collaborators M. Sotomayor, Ohio State University and Vincent Lynch, University of Chicago)

At the interface between physics and molecular and evolutionary biology, we explore the mechanical evolution of adhesion complexes using inner-ear cadherin tip-links as a model system [1]. This project is a collaboration between Marcos SOTOMAYOR (Ohio State University, OH, USA), Vincent LYNCH (University of Chicago, IL, USA) and Felix RICO (Aix-Marseille University, France). We sequence, synthesize, and study tip‐link proteins from diverse extant species and carry out evolutionary analyses both to reconstruct the sequences of ancestral, “resurrected” tip links, and to identify potentially stronger tip links from species in which positive selection is reported. We then use high-speed atomic force microscopy (HS-AFM [2]) to probe the mechanical response of cadherin tip links from different extant species and “resurrected” sequences. High‐speed force spectroscopy [3,4] and molecular dynamics simulations [5] will be combined at similar loading rates to obtain an atomistic description of tip-link mechanics.

[1]        M. Sotomayor, W. A. Weihofen, R. Gaudet, and D. P. Corey, Nature (2012).
[2]        T. Ando, N. Kodera, E. Takai, D. Maruyama, K. Saito, and A. Toda, Proceedings of the National Academy of Sciences 98, 12468 (2001).
[3]        F. Rico, L. Gonzalez, I. Casuso, M. Puig-Vidal, and S. Scheuring, Science 342, 741 (2013).
[4]        F. Sumbul, A. Marchesi, H. Takahashi, S. Scheuring, and F. Rico, in Nanoscale Imaging: Methods and Protocols, edited by Y. L. Lyubchenko (Springer New York, New York, NY, 2018), pp. 243–264.
[5]        M. Sotomayor and K. Schulten, Science 316, 1144 (2007).

logo-blue-6x6-HFSP.jpgThe project is funded by the Human Frontier Science Program (HFSP)