Mechanochemitry: A Molecular Biomechanics View of Mechanosensing

Zhu, Cheng

doi:10.1007/s10439-013-0904-5

Cited by 28 publications

(22 citation statements)

References 115 publications

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“…3e-i). Unlike previously described catch bond or cooperative binding cofactors 33,58 , such as allosteric regulation by neighbouring protein domains (that is, within the molecule) or soluble co-factors, our finding is distinct: the co-factor is a nearby co-receptor but not covalently associated with the first. Importantly, as circulating tumour cells are exposed to a complex haemodynamic environment during the their transit through the vasculature 59 , forces applied to non-covalent interactions between adhesion receptors are important perturbations that may regulate bond affinities and subsequent signalling.…”

Section: Discussioncontrasting

confidence: 80%

“…Singlemolecule approaches (that is, the biomembrane force probe (BFP)) have been extensively used to study force regulation of protein-protein interactions, determine protein conformational changes and understand signal initiation [28][29][30][31] , dissecting the relative contribution of individual proteins from complex molecular cohorts 32 . For example, single-molecule studies have elucidated the catch bond behaviour-bonds can be stabilized rather than disrupted by force 33,34 . Catch bonds are probably essential to key cell physiological events that occur in conditions where forces are externally applied or internally generated by the cell, such as adhesion enhancement of circulating cells and bacteria under shear stress or during receptor mechanosignalling [35][36][37] .…”

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confidence: 99%

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Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

Fiore

Chen

et al. 2014

Nat Commun

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Cancer cell adhesion to the vascular endothelium is a critical step of tumour metastasis. Endothelial surface molecule Thy-1 (CD90) is implicated in the metastatic process through its interactions with integrins and syndecans. However, how Thy-1 supports cell-cell adhesion in a dynamic mechanical environment is not known. Here we show that Thy-1 supports b 1 integrin-and syndecan-4 (Syn4)-mediated contractility-dependent mechanosignalling of melanoma cells. At the single-molecule level, Thy-1 is capable of independently binding a 5 b 1 integrin and syndecan-4 (Syn4) receptors. However, in the presence of both a 5 b 1 and Syn4, the two receptors bind cooperatively to Thy-1, to form a trimolecular complex. This trimolecular complex displays a unique phenomenon we coin 'dynamic catch', characterized by abrupt bond stiffening followed by the formation of catch bonds, where force prolongs the bond lifetime. Thus, we reveal a new class of trimolecular interactions where force strengthens the synergistic binding of two co-receptors and modulates downstream mechanosignalling.

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Section: Discussioncontrasting

confidence: 80%

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confidence: 99%

Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

Fiore

Chen

et al. 2014

Nat Commun

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“…Catch bond, a counterintuitive behavior where force strengthens the molecular interaction as opposed to slip bond that weakens it, has been suggested to provide a potential mechanosensing mechanism (9, 35, 36). We found that increasing approach/retraction speed by shortening the approach/retraction segments of the contact cycle triggered lower level of calcium in T cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Accumulation of Serial Forces on TCR and CD8 Frequently Applied by Agonist Antigenic Peptides Embedded in MHC Molecules Triggers Calcium in T Cells

Pryshchep

Zarnitsyna

Hong

et al. 2014

The Journal of Immunology

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T cell activation by antigen is one of the key events in adaptive immunity. It is triggered by interactions of the T-cell receptor (TCR) and coreceptor (CD8 or CD4) with antigenic peptides embedded in the major histocompatibility complex (pMHC) molecules expressed on antigen presenting cells (APCs). The mechanism of how signal is initiated remains unclear. Here we complement our two-dimensional (2D) kinetic analysis of TCR–pMHC–CD8 interaction with concurrent calcium imaging to examine how ligand engagement of TCR with and without the coengagement of CD8 initiates signaling. We found that accumulation of frequently applied forces on the TCR via agonist pMHC triggered calcium, which was further enhanced by CD8 cooperative binding. Prolonging the intermission between sequential force application simpaired calcium signals. Our data support a model where rapid accumulation of serial forces on TCR–pMHC–CD8 bonds triggers calcium in T cells.

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“…Bell's 1978 paper is generally taken as the seminal starting point, although occasionally earlier work by Zhurkov and Eyring is cited. Mechanochemistry is now being applied to a wide range of areas of chemistry and biochemistry, including solvent free synthesis routes [108,111], molecular motors [112,113], single molecule studies, for example using molecular tweezers or AFMs [114,115], cell differentiation [116,117], and mechanophores [118,119]. The latter are molecular groups designed specifically to respond to mechanical force, to enable this force to be measured externally (sensors) or to produce materials that respond in desired ways to applied forces (smart materials).…”

Section: If Dry Chloride Of Silver In Powder Be Triturated In a Mortamentioning

confidence: 99%

Stress-augmented thermal activation: Tribology feels the force

2018

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Abstract:In stress-augmented thermal activation, the activation energy barrier that controls the rate of atomic and molecular processes is reduced by the application of stress, with the result that the rate of these processes increases exponentially with applied stress. This concept has particular relevance to Tribology, and since its development in the early twentieth century, it has been applied to develop important models of plastic flow, sliding friction, rheology, wear, and tribochemistry. This paper reviews the development of stress-augmented thermal activation and its application to all of these areas of Tribology. The strengths and limitations of the approach are then discussed and future directions considered. From the scientific point of view, the concept of stress-augmented thermal activation is important since it enables the development of models that describe macroscale tribological performance, such as friction coefficient or tribofilm formation, in terms of the structure and behaviour of individual atoms and molecules. This both helps us understand these processes at a fundamental level and also provides tools for the informed design of lubricants and surfaces.

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Mechanochemitry: A Molecular Biomechanics View of Mechanosensing

Cited by 28 publications

References 115 publications

Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

Accumulation of Serial Forces on TCR and CD8 Frequently Applied by Agonist Antigenic Peptides Embedded in MHC Molecules Triggers Calcium in T Cells

Stress-augmented thermal activation: Tribology feels the force

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