Force-dependent recruitment of Piezo1 drives adhesion maturation and calcium entry in normal but not tumor cells

Yao, Mingxi; Tijore, Ajay; Cox, Charles D.; Hariharan, Anushya; Nhieu, Guy Tran Van; Martinac, Boris; Sheetz, Michael P.

doi:10.1101/2020.03.09.972307

Cited by 23 publications

(27 citation statements)

References 92 publications

(199 reference statements)

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“…4). A recent study has shown that Piezo1 is recruited to FAs in normal cells but not in transformed cells including HEK (Yao et al, 2020), that observation was done on a uniform substrate, consistent with our control cells.…”

Section: Discussionsupporting

confidence: 92%

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Adherent cell remodeling on micropatterns is modulated by Piezo1 channels

Jetta

Fard

Sachs

et al. 2020

Preprint

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Adherent cells utilize local environmental cues to make decisions on their growth and movement. We have previously shown that HEK293 cells grown on the fibronectin stripe patterns were elongated. Here we show that Piezo1 function is involved in cell spreading. Inhibiting the Rho-ROCK pathway also reversibly inhibited cell extension indicating that myosin contractility is involved. Piezo1 expressing HEK cells plated on fibronectin stripes elongated, while a knockout of Piezo1 eliminated elongation. Inhibiting Piezo1 conductance using GsMTx4 or Gd3+ blocked cell spreading, but the cells grew thin tail-like extensions along the patterns. Images of GFP-tagged Piezo1 showed plaques of Piezo1 moving to the extrusion edges, co-localized with focal adhesions. Surprisingly, in non-spreading cells Piezo1 was located primarily on the nuclear envelope. The growth of thin extrusion tails did not occur in Piezo1 knockout cells suggesting that Piezo1 may have functions besides acting as a cation channel.

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Section: Discussionsupporting

confidence: 92%

“…4c). Piezo1 can be recruited to FAs(Yao et al, 2020), our results show that co-localization of Piezo1 and FAs does not occur when the cells are in the relaxed state.…”

Section: Resultsmentioning

confidence: 79%

Adherent cell remodeling on micropatterns is modulated by Piezo1 channels

Jetta

Fard

Sachs

et al. 2020

Preprint

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“…Their main advantage for our study is that they can be easily transfected with large constructs like Piezo1 (2521 amino acids, Uniprot entry Q92508) while endogenous Piezo1 expression level is low. Publications connecting Piezo1 to mechano-signaling mediated by integrins are based mainly on Piezo1-mediated elevation of intracellular Ca 2+ , entering the cytosol either from the extracellular space [ 57 ] or from the endoplasmic reticulum [ 29 ]. As PiCS is not suppressed in our hands by blocking Piezo1 ion channel activity using antibiotics, including streptomycin, it is unlikely that Ca 2+ influx via the plasma membrane is required for PiCS and matrix stiffness sensing.…”

Section: Discussionmentioning

confidence: 99%

Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing

Emig

Knodt

Krussig

et al. 2021

Cells

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The mechanical environment of cardiac cells changes continuously and undergoes major alterations during diseases. Most cardiac diseases, including atrial fibrillation, are accompanied by fibrosis which can impair both electrical and mechanical function of the heart. A key characteristic of fibrotic tissue is excessive accumulation of extracellular matrix, leading to increased tissue stiffness. Cells are known to respond to changes in their mechanical environment, but the molecular mechanisms underlying this ability are incompletely understood. We used cell culture systems and hydrogels with tunable stiffness, combined with advanced biophysical and imaging techniques, to elucidate the roles of the stretch-activated channel Piezo1 in human atrial fibroblast mechano-sensing. Changing the expression level of Piezo1 revealed that this mechano-sensor contributes to the organization of the cytoskeleton, affecting mechanical properties of human embryonic kidney cells and human atrial fibroblasts. Our results suggest that this response is independent of Piezo1-mediated ion conduction at the plasma membrane, and mediated in part by components of the integrin pathway. Further, we show that Piezo1 is instrumental for fibroblast adaptation to changes in matrix stiffness, and that Piezo1-induced cell stiffening is transmitted in a paracrine manner to other cells by a signaling mechanism requiring interleukin-6. Piezo1 may be a new candidate for targeted interference with cardiac fibroblast function.

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“…Recent studies have reported the association of Piezo1 with peripheral mature adhesion. 23,24 Hence, we examined if ultrasound treatment promoted Piezo1 translocation to the peripheral adhesions located in the plasma membrane of tumor cells. Cells transiently transfected with mApple-paxillin were used to determine the adhesion distribution.…”

Section: Piezo1 Channel Mediated-calcium Influx Is Required For Tumormentioning

confidence: 99%

Ultrasound-mediated mechanical forces selectively kill tumor cells

Tijore

Margadant

Yao

et al. 2020

Preprint

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Ultrasound has been used to target tumors either through local heating or local nanobubbles but these methods damage surrounding normal cells in the target area. Recent studies show that tumor cells are susceptible to mechanical stresses and undergo calcium-dependent apoptosis under conditions that promote normal cell growth. Here we report that low-frequency ultrasound causes apoptosis of tumor cells by activating a calpain-dependent mitochondrial pathway that depends upon calcium entry through the mechanosensitive Piezo1 channels. This is a general property of all tumor cell lines tested so far irrespective of tissue origin. In animals, ultrasound irradiation causes tumor killing in the chick chorioallantoic membrane (CAM) model with relatively little damage to the chick embryos. Further, patient-derived pancreatic tumor organoids are killed by ultrasound treatment. Because low-level ultrasound causes apoptosis of tumor cells from many different tissues in different microenvironments, it may offer a safe non-invasive approach to augment tumor treatments.

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Force-dependent recruitment of Piezo1 drives adhesion maturation and calcium entry in normal but not tumor cells

Cited by 23 publications

References 92 publications

Adherent cell remodeling on micropatterns is modulated by Piezo1 channels

Adherent cell remodeling on micropatterns is modulated by Piezo1 channels

Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing

Ultrasound-mediated mechanical forces selectively kill tumor cells

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