title: Phenomenological and microscopic theories for catch bonds.
abstract: Lifetimes of bound states of protein complexes or biomolecule folded states typically decrease when subject to mechanical force. However, a plethora of biological systems exhibit the counter-intuitive phenomenon of catch bonding, where non-covalent bonds become stronger under externally applied forces. The quest to understand the origin of catch-bond behavior has led to the development of phenomenological and microscopic theories that can quantitatively recapitulate experimental data. Here, we assess the successes and limitations of such theories in explaining experimental data. The most widely applied approach is a phenomenological two-state model, which fits all of the available data on a variety of complexes: actomyosin, kinetochore-microtubule, selectin-ligand, and cadherin-catenin binding to filamentous actin. With a primary focus on the selectin family of cell-adhesion complexes, we discuss the positives and negatives of phenomenological models and the importance of evaluating the physical relevance of fitting parameters. We describe a microscopic theory for selectins, which provides a structural basis for catch bonds and predicts a crucial allosteric role for residues Asn82-Glu88. We emphasize the need for new theories and simulations that can mimic experimental conditions, given the complex response of cell adhesion complexes to force and their potential role in a variety of biological contexts.
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, United States. Electronic address: shaon@jimmy.harvard.edu.
authors.forename: Shaon
authors.initials: S
authors.lastname: Chakrabarti
authors.affiliation: Department of Physics, Case Western Reserve University, OH 44106, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Hinczewski
authors.affiliation: Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, United States.
authors.forename: D
authors.initials: D
authors.lastname: Thirumalai
mesh_terms: D000205:Actomyosin / Q000737:chemistry; D015820:Cadherins / Q000737:chemistry; D051177:Catenins / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology*; D018386:Kinetochores / Q000737:chemistry; D008024:Ligands; D008962:Models, Theoretical; D011485:Protein Binding; D019087:Selectins / Q000737:chemistry
chemical_list: D015820:Cadherins; D051177:Catenins; D008024:Ligands; D019087:Selectins; D000205:Actomyosin
keywords: Catch-bond; Cell adhesion; Energy landscape; Force