Principles of Mechanosensing at the Membrane Interface

Bavi, Navid; Nikolaev, Yu. A.; Bavi, Omid; Ridone, Pietro; Martinac, Adam D.; Nakayama, Yoshitaka; Cox, Charles D.; Martinac, Boris

doi:10.1007/978-981-10-6244-5_4

Cited by 18 publications

(14 citation statements)

References 227 publications

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“…Activation curvature of MscL, upon addition of TFE from either side, seems consistent with its cylindrical shape. MscS and Piezo1, which are both conical, were only activated from the extracellular side, while the activation of TREK-1 by TFE added to the cytoplasmic side was equally consistent with the curved membrane conforming to its non-planar curved shape (Bavi et al 2017a). In addition, MD simulations revealed that TFE increased the asymmetry of the transbilayer pressure profile markedly, indicating a close relationship between MS channel shapes and their activation mechanism by surface tension perturbations (Bavi et al 2017b).…”

Section: Mscl Piezo1mentioning

confidence: 78%

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Tuning ion channel mechanosensitivity by asymmetry of the transbilayer pressure profile

et al. 2018

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Mechanical stimuli acting on the cellular membrane are linked to intracellular signaling events and downstream effectors via different mechanoreceptors. Mechanosensitive (MS) ion channels are the fastest known primary mechano-electrical transducers, which convert mechanical stimuli into meaningful intracellular signals on a submillisecond time scale. Much of our understanding of the biophysical principles that underlie and regulate conversion of mechanical force into conformational changes in MS channels comes from studies based on MS channel reconstitution into lipid bilayers. The bilayer reconstitution methods have enabled researchers to investigate the structure-function relationship in MS channels and probe their specific interactions with their membrane lipid environment. This brief review focuses on close interactions between MS channels and the lipid bilayer and emphasizes the central role that the transbilayer pressure profile plays in mechanosensitivity and gating of these fascinating membrane proteins.

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Section: Mscl Piezo1mentioning

confidence: 78%

“…The anisotropy of the transbilayer pressure profile results from mainly three factors explained in Fig. 3a (Bavi et al 2017a). There is repulsion between the head groups and steric repulsion in the tails, which is strongly dependent on the degree of lipid saturation (Ridone et al 2018).…”

Section: Transbilayer Pressure Profilementioning

confidence: 99%

Tuning ion channel mechanosensitivity by asymmetry of the transbilayer pressure profile

et al. 2018

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“…This indicates that ion channel mechanosensitivity exists in different forms, with local membrane curvature being one of them. Although membrane stretch and local membrane curvature are mechanical stimuli that activate mechanosensitive channels, such as MscL, MscS, TREK-1, TRAAK and Piezo1 (Bavi et al, 2017), this does not seem to be the case for other ion channels, such as TRPC6, which may be able to differentiate between these two kinds of mechanical stimulus. Further to this point, it is important to note that even homologues of the prototypical mechanosensitive channel MscL exhibit a different sensitivity to membrane stretch and curvature, despite their high degree of sequence similarity (Mukherjee et al, 2014).…”

Section: Coreymentioning

confidence: 99%

Mammalian TRP ion channels are insensitive to membrane stretch

Nikolaev

Cox

Ridone

et al. 2019

Journal of Cell Science

127

105

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TRP channels of the transient receptor potential ion channel superfamily are involved in a wide variety of mechanosensory processes, including touch sensation, pain, blood pressure regulation, bone loading and detection of cerebrospinal fluid flow. However, in many instances it is unclear whether TRP channels are the primary transducers of mechanical force in these processes. In this study, we tested stretch activation of eleven TRP channels from six mammalian subfamilies. We found that these TRP channels were insensitive to short membrane stretches in cellular systems. Furthermore, we purified TRPC6 and demonstrated its insensitivity to stretch in liposomes, an artificial bilayer system free from cellular components. Additionally, we demonstrated that, when expressed in C. elegans neurons, mouse TRPC6 restores the mechanoresponse of a touch insensitive mutant but requires diacylglycerol for activation. These results strongly suggest that the mammalian members of the TRP ion channel family are insensitive to tension induced by cell membrane stretching and, thus, are more likely to be activated by cytoplasmic tethers or downstream components and to act as amplifiers of cellular mechanosensory signaling cascades.

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“…Neurons and glia are highly mechanosensitive ( Previtera et al, 2010 ; Blumenthal et al, 2014 ) and detect changes in the stiffness of underlying cell culture substrates via stretch-activated membrane-spanning ion channels ( Cox et al, 2016 ; Bavi et al, 2017 ). Microglial cells, for example, display durotaxis, i.e., they migrate toward stiffer areas when cultured on stiffness gradient hydrogels ( Bollmann et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes

Velasco‐Estevez

Mampay

Boutin

et al. 2018

Front. Aging Neurosci.

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A defining pathophysiological hallmark of Alzheimer’s disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Aβ1-42 peptides. Amyloid plaques are hard, brittle structures scattered throughout the hippocampus and cerebral cortex and are thought to cause hyperphosphorylation of tau, neurofibrillary tangles, and progressive neurodegeneration. Reactive astrocytes and microglia envelop the exterior of amyloid plaques and infiltrate their inner core. Glia are highly mechanosensitive cells and can almost certainly sense the mismatch between the normally soft mechanical environment of the brain and very stiff amyloid plaques via mechanosensing ion channels. Piezo1, a non-selective cation channel, can translate extracellular mechanical forces to intracellular molecular signaling cascades through a process known as mechanotransduction. Here, we utilized an aging transgenic rat model of AD (TgF344-AD) to study expression of mechanosensing Piezo1 ion channels in amyloid plaque-reactive astrocytes. We found that Piezo1 is upregulated with age in the hippocampus and cortex of 18-month old wild-type rats. However, more striking increases in Piezo1 were measured in the hippocampus of TgF344-AD rats compared to age-matched wild-type controls. Interestingly, repeated urinary tract infections with Escherichia coli bacteria, a common comorbidity in elderly people with dementia, caused further elevations in Piezo1 channel expression in the hippocampus and cortex of TgF344-AD rats. Taken together, we report that aging and peripheral infection augment amyloid plaque-induced upregulation of mechanoresponsive ion channels, such as Piezo1, in astrocytes. Further research is required to investigate the role of astrocytic Piezo1 in the Alzheimer’s brain, whether modulating channel opening will protect or exacerbate the disease state, and most importantly, if Piezo1 could prove to be a novel drug target for age-related dementia.

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Principles of Mechanosensing at the Membrane Interface

Cited by 18 publications

References 227 publications

Tuning ion channel mechanosensitivity by asymmetry of the transbilayer pressure profile

Tuning ion channel mechanosensitivity by asymmetry of the transbilayer pressure profile

Mammalian TRP ion channels are insensitive to membrane stretch

Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes

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