title: Two-bubble acoustic tweezing cytometry for biomechanical probing and stimulation of cells.
abstract: The study of mechanotransduction relies on tools that are capable of applying mechanical forces to elicit and assess cellular responses. Here we report a new (to our knowledge) technique, called two-bubble acoustic tweezing cytometry (TB-ATC), for generating spatiotemporally controlled subcellular mechanical forces on live cells by acoustic actuation of paired microbubbles targeted to the cell adhesion receptor integrin. By measuring the ultrasound-induced activities of cell-bound microbubbles and the actin cytoskeleton contractile force responses, we determine that TB-ATC elicits mechanoresponsive cellular changes via cyclic, paired displacements of integrin-bound microbubbles driven by the attractive secondary acoustic radiation force (sARF) between the bubbles in an ultrasound field. We demonstrate the feasibility of dual-mode TB-ATC for both subcellular probing and mechanical stimulation. By exploiting the robust and unique interaction of ultrasound with microbubbles, TB-ATC provides distinct advantages for experimentation and quantification of applied forces and cellular responses for biomechanical probing and stimulation of cells.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Yubing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Madhu S R
authors.initials: MS
authors.lastname: Gudur
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Yi-Sing
authors.initials: YS
authors.lastname: Hsiao
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan. Electronic address: jpfu@umich.edu.
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan. Electronic address: cxdeng@umich.edu.
authors.forename: Cheri X
authors.initials: CX
authors.lastname: Deng
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D003584:Cytological Techniques / Q000379:methods*; D003599:Cytoskeleton / Q000502:physiology; D005240:Feasibility Studies; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000737:chemistry; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008853:Microscopy; D041681:NIH 3T3 Cells; D014465:Ultrasonics / Q000379:methods*; D014741:Video Recording
chemical_list: D000199:Actins; D016023:Integrins