안성철 (The State University of New Jersey) | 한빛사논문 > 한빛사

한빛사논문

조회640

The State University of New Jersey

CV File 154 kb

ACS Nano, Publication Date:July 1, 2021 | https://doi.org/10.1021/acsnano.1c01782 Molecular Nanomechanical Mapping of Histamine-Induced Smooth Muscle Cell Contraction and Shortening

Myung Hyun Jo,¹ ByoungChoul Kim,^2,3 Keewon Sung,⁴ Reynold A. Panettieri Jr.,⁵ Steven S. An,^5,6,* Jian Liu,^7,* and Taekjip Ha^1,2,8,*

¹Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; ²Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; ³Division of Nano-Bioengineering, Incheon National University, Incheon 22012, South Korea; ⁴Department of Chemistry, Seoul National University, Seoul 08826, South Korea; ⁵Rutgers Institute for Translational Medicine and Science, The State University of New Jersey, New Brunswick, NJ 08901, USA; ⁶Department of Pharmacology, Rutgers-Robert Wood Johnson Medica lSchool, The State University of NewJersey, Piscataway, NJ 08854, USA; ⁷Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, MD 20205, USA; ⁸Howard Hughes Medical Institute, Baltimore, MD 21205, USA.

^*Correspondingauthors

Abstract

Mechanical response to external stimuli is a conserved feature of many cell types. For example, neurotransmitters (e.g., histamine) trigger calcium signals that induce actomyosin-regulated contraction of airway smooth muscle (ASM); the resulting cell shortening causes airway narrowing, the excess of which can cause asthma. Despite intensive studies, however, it remains unclear how physical forces are propagated through focal adhesion (FA)—the major force-transmission machinery of the cell—during ASM shortening. We provide a nanomechanical platform to directly image single molecule forces during ASM cell shortening by repurposing DNA tension sensors. Surprisingly, cell shortening and FA disassembly that immediately precedes it occurred long after histamine-evoked increases in intracellular calcium levels ([Ca2+]i). Our mathematical model that fully integrates cell edge protrusion and retraction with contractile forces acting on FA predicted that (1) stabilization of FA impedes cell shortening and (2) the disruption of FAs is preceded by their strengthening through actomyosin-activated molecular tension. We confirmed these predictions via real-time imaging and molecular force measurements. Together, our work highlights a key role of FA dynamics in regulating ASM contraction induced by an allergen with potential therapeutic implications.

KEYWORDS : cell contraction, cell shortening, focal adhesion, mechanobiology, muscle biophysics, tension gauge tether, molecular force probe

논문정보

형식Research article
게재일2021년 07월 (BRIC 등록일 2021-07-07)
연구진국내+국외 연구진
분야 생명과학 > 생리학

댓글 작성 로그인

CV 열람하기

연락처 보기