Mechanisms linking mechanotransduction and cell metabolism

Salvi, Alicia M.; DeMali, Kris A.

doi:10.1016/j.ceb.2018.05.004

Cited by 48 publications

(42 citation statements)

References 52 publications

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“…Emerging data indicate a close relationship between mechanotransduction and metabolism [149][150][151]. In response to modification of environmental cues, cells have an intrinsic ability to modulate their metabolism to better match the new energy demands.…”

Section: Mechanotransduction In β-Cells: the Contribution Of Metabolismmentioning

confidence: 99%

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

Galli

Marku

Marciani

et al. 2020

Cells

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Embryonic and pluripotent stem cells hold great promise in generating β-cells for both replacing medicine and novel therapeutic discoveries in diabetes mellitus. However, their differentiation in vitro is still inefficient, and functional studies reveal that most of these β-like cells still fail to fully mirror the adult β-cell physiology. For their proper growth and functioning, β-cells require a very specific environment, the islet niche, which provides a myriad of chemical and physical signals. While the nature and effects of chemical stimuli have been widely characterized, less is known about the mechanical signals. We here review the current status of knowledge of biophysical cues provided by the niche where β-cells normally live and differentiate, and we underline the possible machinery designated for mechanotransduction in β-cells. Although the regulatory mechanisms remain poorly understood, the analysis reveals that β-cells are equipped with all mechanosensors and signaling proteins actively involved in mechanotransduction in other cell types, and they respond to mechanical cues by changing their behavior. By engineering microenvironments mirroring the biophysical niche properties it is possible to elucidate the β-cell mechanotransductive-regulatory mechanisms and to harness them for the promotion of β-cell differentiation capacity in vitro.

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Section: Mechanotransduction In β-Cells: the Contribution Of Metabolismmentioning

confidence: 99%

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

Galli

Marku

Marciani

et al. 2020

Cells

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“…Feedback through mechanoresponsive proteins can occur within timescales from a few seconds to minutes, although the associated feedback loops also function over prolonged periods of time to integrate different cellular processes. Mechanically transduced transcription factors have emerged as key regulators of the feedback between the mechanical state of the cell and changes in gene expression to maintain homeostasis and cellular identity (Broders-Bondon et al, 2018;Salvi and DeMali, 2018;Kassianidou et al, 2019). Among these are the Hippo pathway proteins Yesassociated protein (YAP, also known as YAP1) and transcriptional coactivator with PDZ-motif (TAZ, also known as WWTR1), which regulate E-cadherin junctional organization, chromatin remodeling and even cell metabolism (Panciera et al, 2017).…”

Section: Feedback Across Long Timescalesmentioning

confidence: 99%

“…For example, the application of shear stress or force on E-cadherin at cell-cell junctions results in the activation and recruitment of AMP-activated protein kinase (AMPK) to adhesion complexes, which results in increased phosphorylation and activation of myosin II. This also increases glucose intake and ATP production, providing the cell with increased energy to actively respond to the change in its environment (Bays et al, 2017;Salvi and DeMali, 2018).…”

Section: Feedback Across Long Timescalesmentioning

confidence: 99%

How the mechanobiome drives cell behavior, viewed through the lens of control theory

Kothari

Johnson

Sandone

et al. 2019

Journal of Cell Science

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Cells have evolved sophisticated systems that integrate internal and external inputs to coordinate cell shape changes during processes, such as development, cell identity determination, and cell and tissue homeostasis. Cellular shape-change events are driven by the mechanobiome, the network of macromolecules that allows cells to generate, sense and respond to externally imposed and internally generated forces. Together, these components build the cellular contractility network, which is governed by a control system. Proteins, such as non-muscle myosin II, function as both sensors and actuators, which then link to scaffolding proteins, transcription factors and metabolic proteins to create feedback loops that generate the foundational mechanical properties of the cell and modulate cellular behaviors. In this Review, we highlight proteins that establish and maintain the setpoint, or baseline, for the control system and explore the feedback loops that integrate different cellular processes with cell mechanics. Uncovering the genetic, biophysical and biochemical interactions between these molecular components allows us to apply concepts from control theory to provide a systems-level understanding of cellular processes. Importantly, the actomyosin network has emerged as more than simply a 'downstream' effector of linear signaling pathways. Instead, it is also a significant driver of cellular processes traditionally considered to be 'upstream'.

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“…Much attention has been given to how cells respond to mechanical forces. However, less is known how these forces are integrated with other cellular processes including bioenergetics [11][12][13] . In order to understand how mechanical forces shape the cellular phenotype and regulate cell fate, it is necessary to consider the highly dynamic nature of the cellular response, which involves a hitherto overlooked large energy expenditure.…”

Section: Introductionmentioning

confidence: 99%

“…Actomyosin contractility also plays a major role in the cellular response to the physical properties of the ECM through FA formation and organization of the actin cytoskeleton, which are ATP-dependent 11,12,25,26 . We hypothesized that the very expenditure of ATP during spreading regulates the cellular mechanoresponse to physical cues.…”

Section: Introductionmentioning

confidence: 99%

Energy Expenditure during Cell Spreading Regulates the Stem Cells Responses to Matrix Stiffness

Xie

Bao

Koopman

et al. 2019

Preprint

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Cells respond to the mechanical properties of the extracellular matrix (ECM) through formation of focal adhesions (FAs), re-organization of the actin cytoskeleton and adjustment of cell contractility. These are energy-demanding processes, but a potential causality between mechanical cues and cellular (energy) metabolism remains largely unexplored. Here, we demonstrate that cytoskeletal reorganization and FA formation during cell spreading on stiff substrates lead to a drop in intracellular ATP levels, thereby activating AMP-activated protein kinase (AMPK). The latter then triggers rapid mitochondrial fragmentation and an increase in ATP levels to reinforce cell tension and regulate nuclear localization of YAP/TAZ and Runx2.Genetic ablation of AMPK Thr-172 phosphorylation lowered cellular ATP content and strongly reduced responses to substrate stiffness. Together, these findings reveal the importance of energy expenditure in regulating the mechanoresponse of cells, and point to AMPK as a key mediator of stem cell fate in response to ECM mechanics.

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Mechanisms linking mechanotransduction and cell metabolism

Cited by 48 publications

References 52 publications

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

How the mechanobiome drives cell behavior, viewed through the lens of control theory

Energy Expenditure during Cell Spreading Regulates the Stem Cells Responses to Matrix Stiffness

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