Deciphering Mechanochemical Influences of Emergent Actomyosin Crosstalk using QCM-D.

ABSTRACT

Cytoskeletal protein ensembles exhibit emergent mechanics where behavior exhibited in teams is not necessarily the sum of the components' single molecule properties. In addition, filaments may act as force sensors that distribute feedback and influence motor protein behavior. To understand the design principles of such emergent mechanics, we developed an approach utilizing QCM-D to measure how actomyosin bundles respond mechanically to environmental variables that alter constituent myosin II motor behavior. We demonstrate that QCM-D can detect changes in actomyosin viscoelasticity due to molecular-level alterations, such as motor concentration and nucleotide state, thus providing evidence for actin's role as a mechanical force-feedback sensor and a new approach for deciphering the fundamental mechanisms of emergent cytoskeletal ensemble crosstalk. Justification Cytoskeletal ensembles exhibit mechanics that are not necessarily the sum of the components' single molecule properties, and this emergent behavior is not well understood. Cytoskeletal filaments may also act as force sensors that influence constituent motor protein behavior. To understand the elusive design principles of such emergent mechanics, we innovated an approach using QCM-D to measure how actomyosin bundles sense and respond mechanically to environmental variables. We demonstrate for the first time that QCM-D can detect changes in actomyosin viscoelasticity due to molecular-level alterations, thus providing evidence for actin's role as a mechanical force-feedback sensor and a new approach for deciphering the fundamentals of emergent cytoskeletal ensemble crosstalk.