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Review
. 2022 Jan 31;45(1):16-25.
doi: 10.14348/molcells.2022.2026.

Nano-Precision Tweezers for Mechanosensitive Proteins and Beyond

Taehyun Yang  1 , Celine Park  1 , Sang-Hyun Rah  1 , Min Ju Shon  1   2
Affiliations
Review

Nano-Precision Tweezers for Mechanosensitive Proteins and Beyond

Taehyun Yang et al. Mol Cells. .

Abstract

Mechanical forces play pivotal roles in regulating cell shape, function, and fate. Key players that govern the mechanobiological interplay are the mechanosensitive proteins found on cell membranes and in cytoskeleton. Their unique nanomechanics can be interrogated using single-molecule tweezers, which can apply controlled forces to the proteins and simultaneously measure the ensuing structural changes. Breakthroughs in high-resolution tweezers have enabled the routine monitoring of nanometer-scale, millisecond dynamics as a function of force. Undoubtedly, the advancement of structural biology will be further fueled by integrating static atomic-resolution structures and their dynamic changes and interactions observed with the force application techniques. In this minireview, we will introduce the general principles of single-molecule tweezers and their recent applications to the studies of force-bearing proteins, including the synaptic proteins that need to be categorized as mechanosensitive in a broad sense. We anticipate that the impact of nano-precision approaches in mechanobiology research will continue to grow in the future.

Keywords: SNARE complex; mechanosensitive proteins; single-molecule tweezers; synapse mechanobiology.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. Principles of single-molecule tweezers.
(A) Schematics of optical and magnetic tweezers for the mechanical studies of protein. (B) Types of force application procedure in single-molecule tweezers with hypothetical data expected from a model protein with three observable states (bottom right). At low forces (<10 pN), the protein is zippered (Z). At intermediates forces (10-15 pN), it unfolds to an intermediate structure (I), and at very high forces (>15 pN) it is completely unzippered (U).
Fig. 2
Fig. 2. Application of single-molecule tweezers to mechanosensitive proteins.
(A) Cellular landscape of mechanosensitivity. Green arrows indicate the typical directions of forces. Representative examples of mechanosensitive proteins that have been studied with single-molecule tweezers are shown. (B) Different modes of mechanical allostery in protein conformation change.
Fig. 3
Fig. 3. Application of single-molecule tweezers to synaptic mechanosensitivity.
(A) Mechanobiological landscape of a neuronal synapse. (B) Protein machinery for synaptic vesicle trafficking. Representative proteins participating in the different stages of vesicle trafficking are shown. (C) High-resolution magnetic tweezer study of SNARE complex dynamics and the effect of complexin (Cpx). Adapted from the article of Shon et al. (2018) (Nat. Commun. 9, 3639) under Creative Commons Attribution (CC BY 4.0) license. (D) Optical tweezer study on the effect of α-SNAP binding to SNARE complex. Adapted from the article of Ma et al. (2016) (Cell Rep. 15, 531-539) under Creative Commons Attribution (CC BY 4.0) license. (E) High-speed observations of α-SNAP/NSF-mediated SNARE complex disassembly using magnetic tweezers. Adapted from the article of Kim et al. (2021) (Nat. Commun. 12, 3206) under Creative Commons Attribution (CC BY 4.0) license.
See this image and copyright information in PMC

References

    1. Arbore C., Perego L., Sergides M., Capitanio M. Probing force in living cells with optical tweezers: from single-molecule mechanics to cell mechanotransduction. Biophys. Rev. 2019;11:765–782. doi: 10.1007/s12551-019-00599-y. - DOI - PMC - PubMed
    1. Arya M., Anvari B., Romo G.M., Cruz M.A., Dong J.F., McIntire L.V., Moake J.L., López J.A. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood. 2002;99:3971–3977. doi: 10.1182/blood-2001-11-0060. - DOI - PubMed
    1. Austen K., Ringer P., Mehlich A., Chrostek-Grashoff A., Kluger C., Klingner C., Sabass B., Zent R., Rief M., Grashoff C. Extracellular rigidity sensing by talin isoform-specific mechanical linkages. Nat. Cell Biol. 2015;17:1597–1606. doi: 10.1038/ncb3268. - DOI - PMC - PubMed
    1. Brunger A.T., Choi U.B., Lai Y., Leitz J., Zhou Q. Molecular mechanisms of fast neurotransmitter release. Annu. Rev. Biophys. 2018;47:469–497. doi: 10.1146/annurev-biophys-070816-034117. - DOI - PMC - PubMed
    1. Buckley C.D., Tan J., Anderson K.L., Hanein D., Volkmann N., Weis W.I., Nelson W.J., Dunn A.R. Cell adhesion. The minimal cadherin-catenin complex binds to actin filaments under force. Science. 2014;346:1254211. doi: 10.1126/science.1254211. - DOI - PMC - PubMed

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