title: Acoustic tweezing cytometry for live-cell subcellular modulation of intracellular cytoskeleton contractility.
abstract: Mechanical forces are critical to modulate cell spreading, contractility, gene expression, and even stem cell differentiation. Yet, existing tools that can apply controllable subcellular forces to a large number of single cells simultaneously are still limited. Here we report a novel ultrasound tweezing cytometry utilizing ultrasound pulses to actuate functionalized lipid microbubbles covalently attached to single live cells to exert mechanical forces in the pN - nN range. Ultrasonic excitation of microbubbles could elicit a rapid and sustained reactive intracellular cytoskeleton contractile force increase in different adherent mechanosensitive cells. Further, ultrasound-mediated intracellular cytoskeleton contractility enhancement was dose-dependent and required an intact actin cytoskeleton as well as RhoA/ROCK signaling. Our results demonstrated the great potential of ultrasound tweezing cytometry technique using functionalized microbubbles as an actuatable, biocompatible, and multifunctional agent for biomechanical stimulations of cells.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Fan
authors.forename: Yubing
authors.initials: Y
authors.lastname: Sun
authors.lastname: Di Chen
authors.forename: Donald
authors.initials: D
authors.lastname: Tay
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.forename: Cheri X
authors.initials: CX
authors.lastname: Deng
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D024462:Myosin Type II / Q000378:metabolism; D033081:Shear Strength; D015398:Signal Transduction; D013016:Sound; D013314:Stress, Mechanical; D059008:Time-Lapse Imaging; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D024462:Myosin Type II; D020742:rhoA GTP-Binding Protein; D002118:Calcium