The biophysics of piezo1 and piezo2 mechanosensitive channels

Soattin, Luca; Fiore, Michele; Gavazzo, Paola; Viti, Federica; Facci, Paolo; Raiteri, Roberto; Difato, Francesco; Pusch, Michael; Vassalli, Massimo

doi:10.1016/j.bpc.2015.06.013

Cited by 25 publications

(23 citation statements)

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“…Both piezo1 and piezo2 channels are cation selective mechanical channels with a selectivity sequence of Ca 2 + > K + > Na + > Mg 2 + [21, 22]. In primary articular chondrocytes, expression of Piezo1 and −2 induces Ca 2+ signals and electrical currents.…”

Section: Discussionmentioning

confidence: 99%

Piezo2 protein: A novel regulator of tumor angiogenesis and hyperpermeability

et al. 2016

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Angiogenesis is important for invasive tumor growth and metastasis. Its inhibition is a promising tactic for limiting tumor progression. Here, we showed that Piezo2 knockdown led to decreased glioma angiogenesis and reduced vascular hyperpermeability. Piezo2 was highly expressed in tumor endothelial cells, and its knockdown suppressed vascular leakage and tumor angiogenesis. In a retinal vasculature development assay, corneal angiogenesis assay and a modified Miles assay, Piezo2 knockdown obviously decreased angiogenesis and vascular hyperpermeability. In vitro assays revealed that Piezo2 knockdown inhibited endothelial cell proliferation, migration, and tube formation. Moreover, In vitro co-culture system assay showed that Piezo2 knockdown in endothelial cells suppressed cell proliferation, migration, and invasion of glioma tumor cells. Piezo2 could regulate glioma angiogenesis via Ca2+/Wnt11/β-catenin signaling in endothelial cells. Taken together, these studies provide the evidence for Piezo2 as a critical regulator of tumor angiogenesis and vascular permeability.

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Section: Discussionmentioning

confidence: 99%

Piezo2 protein: A novel regulator of tumor angiogenesis and hyperpermeability

et al. 2016

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“…Piezo proteins contain between 2500 and 2800 amino acids and a number of transmembrane domains between 24 and 40. They are also subjected to homo‐multimerization, likely as tetramers, resulting in large channels with 120 to 160 transmembrane segments . Due to the large size of piezo proteins, crystallographic analysis represents a formidable technical challenge.…”

Section: Touchmentioning

confidence: 99%

“…The first model suggests the formation of one central pore formed at the boundary of the monomers, in the second model each monomer in the tetrameric assembly can contain its proper ion conducting pore. In this case, mechanosensitivity could be an independent function of each monomer or could be related to the ion channel assembly . Both Piezo 1 and Piezo 2 are cation selective with a selectivity sequence of Ca 2+ >K + >Na + >Mg 2+ .…”

Section: Touchmentioning

confidence: 99%

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Sensor Devices Inspired by the Five Senses: A Review

Svechtarova¹,

Buzzacchera²,

Toebes³

et al. 2016

Electroanalysis

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1IntroductionWearable sensor technology is at the forefront of popular media and at the same time is the subject of intense activity in the scientific world. Thes cientificallyd rivenq uantified self focuseso nc ollecting data on the human state to gather information to improve quality of life,t he more extreme end of the spectrume ncompasses biohacktivism and the post-humanist grinderm ovementa dvocating the use of DIY implants to augment the human body to at ranshuman state. [1][2][3][4][5][6][7][8][9][10][11][12][13].T he focus of the current state of the mainstreama rt rests in augmenting the body with ar ange of relatively simplistica rtificial sensors such as temperature,a ccelerometers for posture and motion, electrocardiology,a nd basic chemical sensors sucha sg lucose monitors.I nf act the body is already at reasure-trove of informationa nd integrated sensor systems that are waitingt ob et apped by the next generation of wearable sensor devices.T he human brain like am odern computer or smartphone,c an process thousands of signals from various inputs in an instant. These primary senses were first definedb yA ristotle in Sense and Sensebilia [14] however it was rather Plato in Theateus that first postulated to humansa nd animals being an etwork of "perceptions" when Socratess tatedt hat "The nameless ones are unlimited in number, but those which have been given names are extremely numerous" [15].J ust as am odern smartphone incorporates multiple sensors such as gyroscope, accelerometer, magnetometer and barometers in concert to accurately determine,a ggregate and presents implified locationa nd orientation information to the end user each of the five traditional perceptionsa re the result of multiple sensory functionsw ithin the human body.Fort he purpose of thisr eview we classify the multitude of sensory systems into the Aristotle model of five key senses used to gather information about the outside world. Theh uman body represents an immense source of data collection aggregation and archiving relating to surroundings,b iochemical and temporal processes that allow the brain to understand the environment and its effecto n the body in real time.T he potential to access such ah uge reservoir of data that can be captured from existing bodily sensor systems is the next greatest challengei n sensor development. Rather than develop ever more complicated sensor devices the biggest challenge is how to interface with the existing bodily data streams and harvestt his information to aid in diagnostics,h ealth and wellbeing.Between detectiona nd conscious sensationt herei so ne more essential step that holds the key to accessing the human big data set:d igitalization. In computer terms this is what happens between the first tap of ak ey on ak eyboard and its visualization on the computers creen.W ith computers the processi sr elatively simple,p ushingakey simply closes ac ircuit generating ac urrentt hat travels to the processing unit, where its unique pattern is decoded and translated to the character [16].Inthe b...

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“…However, this hypothesis has not been validated with biophysical experiments, and there is speculation that they might not be traditional mechanosensitive channels at all, activated by a cytoskeletal structure instead (Soattin et al, 2016). Despite their broad medical significance (Coste et al, 2012;Gottlieb & Sachs, 2012;Soattin et al, 2016), their biophysical and physiological properties are poorly understood and remain to be studied.…”

Section: Mechanosensitive Channels In Higher-order Organismsmentioning

confidence: 99%

Biophysical and Structural Studies of Escherichia coli Mechanosensitive Channel of Large Conductance in Lipid Bilayers

Chi¹

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A major challenge of drug development is maximising specificity and efficacy at the lowest possible dose to minimise toxic side effects (Basile et al., 2012). Not only are the pharmaceutical windows small for both drug candidates and approved drugs alike, but they can also vary between individuals, making a dose level safe for one individual potentially harmful for another. One strategy for overcoming this problem is to develop new drug delivery methods where the drug is preferentially concentrated at the site of disease (Basile et al., 2012). In this respect, liposomal drug delivery systems have been used with success in topical applications in skin cancer treatment, and there is significant research interest in engineering similar systems for intravenous administration (Al-Jamal & Kostarelos, 2011;Fan & Zhang, 2013). Incorporating nanovalves into liposomes with controllable gating properties would further enhance the usefulness of liposomal drug delivery systems, providing a method to further regulate the release of liposome-encapsulated drugs from liposomes at the target site (Martinac et al., 2014).The mechanosensitive channel of large conductance (MscL) has been identified as a major candidate for the development of a protein-based nanovalve (Martinac et al., 2014). More generally, MscL is a prototype for the class of ion channels primarily gated by membrane tension, which includes medically significant proteins such as Piezo channels and TRP-type sodium channels (Martinac, 2011). As a well-expressing protein from Escherichia coli, MscL has been extensively studied both structurally and biophysically (Martinac, 2011). However, the channel gating mechanism of MscL, and by extension of mechanosensitive channels in general, remains poorly understood at the molecular level.This thesis aims to investigate the relationship between E. coli MscL and phospholipids both in the context of its structure and its behaviour in a lipid bilayer environment. While much has been studied on the channel gating properties of MscL in various phospholipid environments (Anishkin et al., 2005;Iscla et al., 2004;Iscla et al., 2011;Powl et al., 2008b;Tsai et al., 2005;Yoshimura et al., 2004), there remains a limited understanding of the behaviour and distribution of MscL in the bilayer. These are not only important from academic perspective as well as in the context of nanovalve development, but also for example, to identify factors which may limit the functional studies on MscL. More specifically, this thesis has focused on the identification of phospholipids closely associating with MscL, the distribution of MscL in phospholipid bilayers, and the incorporation of MscL into liposomes with heterogeneous phospholipids.The first research chapter (Chapter 2) outlines the optimisation of MscL expression and purification system for biophysical and structural studies. The original MscL construct had problems of ii heterogeneous expression and being not well-suited to reliable quantification by routine methods.New constructs were suc...

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The biophysics of piezo1 and piezo2 mechanosensitive channels

Cited by 25 publications

References 50 publications

Piezo2 protein: A novel regulator of tumor angiogenesis and hyperpermeability

Piezo2 protein: A novel regulator of tumor angiogenesis and hyperpermeability

Sensor Devices Inspired by the Five Senses: A Review

Biophysical and Structural Studies of Escherichia coli Mechanosensitive Channel of Large Conductance in Lipid Bilayers

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