title: Interplay of active processes modulates tension and drives phase transition in self-renewing, motor-driven cytoskeletal networks.
abstract: The actin cytoskeleton--a complex, nonequilibrium network consisting of filaments, actin-crosslinking proteins (ACPs) and motors--confers cell structure and functionality, from migration to morphogenesis. While the core components are recognized, much less is understood about the behaviour of the integrated, disordered and internally active system with interdependent mechano-chemical component properties. Here we use a Brownian dynamics model that incorporates key and realistic features--specifically actin turnover, ACP (un)binding and motor walking--to reveal the nature and underlying regulatory mechanisms of overarching cytoskeletal states. We generate multi-dimensional maps that show the ratio in activity of these microscopic elements determines diverse global stress profiles and the induction of nonequilibrium morphological phase transition from homogeneous to aggregated networks. In particular, actin turnover dynamics plays a prominent role in tuning stress levels and stabilizing homogeneous morphologies in crosslinked, motor-driven networks. The consequence is versatile functionality, from dynamic steady-state prestress to large, pulsed constrictions.
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, Massachusetts 02215, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mak
authors.affiliation: Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, Massachusetts 02215, USA.|Howard Hughes Medical Institute, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Muhammad H
authors.initials: MH
authors.lastname: Zaman
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette, Indiana 47907, USA.
authors.forename: Taeyoon
authors.initials: T
authors.lastname: Kim
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D045744:Cell Line, Tumor; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D056004:Molecular Dynamics Simulation; D020409:Molecular Motor Proteins / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D044367:Phase Transition; D013314:Stress, Mechanical; D053778:Thiazolidines / Q000494:pharmacology; D059008:Time-Lapse Imaging
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D020409:Molecular Motor Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D053778:Thiazolidines; D015638:Cytochalasin D; C037067:latrunculin A