On the coupling of mechanics with bioelectricity and its role in morphogenesis

Leronni, Alessandro; Bardella, Lorenzo; Dorfmann, Luis; Pietak, Alexis; Levin, Michael

doi:10.1098/rsif.2020.0177

Cited by 16 publications

(11 citation statements)

References 57 publications

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“…If the proposed model is experimentally validated, it can be combined with models of biological cells -Figure 1. Charge density patterns and modulations could asymmetrically influence specific ion pumps' activity, impact attachment to the fiber of proteins driving membrane adhesion 63 and hence guide migration, proliferation patterns and morphogenesis 64 . Exploring those hypotheses is the way forward in understanding the mechanisms underpinning tissue and cell responses to ES.…”

Section: Discussionmentioning

confidence: 99%

Finite Element Modelling of a Cellular Electric Microenvironment

Verdes

Disney

Phamornnak

et al. 2021

JoVE

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Clinical studies show electrical stimulation (ES) to be a potential therapy for the healing and regeneration of various tissues. Understanding the mechanisms of cell response when exposed to electrical fields can therefore guide the optimization of clinical applications. In vitro experiments aim to help uncover those, offering the advantage of wider input and output ranges that can be ethically and effectively assessed. However, the advancements in in vitro experiments are difficult to reproduce directly in clinical settings. Mainly, that is because the ES devices used in vitro differ significantly from the ones suitable for patient use, and the path from the electrodes to the targeted cells is different. Translating the in vitro results into in vivo procedures is therefore not straightforward. We emphasize that the cellular microenvironment's structure and physical properties play a determining role in the actual experimental testing conditions and suggest that measures of charge distribution can be used to bridge the gap between in vitro and in vivo. Considering this, we show how in silico finite element modelling (FEM) can be used to describe the cellular microenvironment and the changes generated by electric field (EF) exposure. We highlight how the EF couples with geometric structure to determine charge distribution. We then show the impact of time dependent inputs on charge movement. Finally, we demonstrate the relevance of our new in silico model methodology using two case studies: (i) in vitro fibrous Poly(3,4ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT-PSS) scaffolds and (ii) in vivo collagen in extracellular matrix (ECM).

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Section: Discussionmentioning

confidence: 99%

Finite Element Modelling of a Cellular Electric Microenvironment

Verdes

Disney

Phamornnak

et al. 2021

JoVE

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“…The model may be quite straightforwardly complemented with the addition of (i) the active transmembrane ion transport through ion pumps, (ii) the dependency of the diffusivity of ion channels and gap junctions on the membrane potential and tension (so as to account for voltage gating and mechanosensitivity), and (iii) genetic and biochemical dynamics required for specific applications, as already addressed in the literature (Pietak and Levin 2016 , 2017 ; Leronni et al. 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…In order to numerically address the coupling between mechanical and bioelectrical signaling, BETSE has been endowed with a solid mechanics module in Leronni et al. ( 2020 ), leading to mecBETSE. Specifically, such a module allows one to compute the cluster deformation due to the osmotic pressure gradients determined by the bioelectrical activity and to account for mechanosensitive channels.…”

Section: Introductionmentioning

confidence: 99%

Modeling the mechanobioelectricity of cell clusters

Leronni

2020

Biomech Model Mechanobiol

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We propose a continuum finite strain theory for the interplay between the bioelectricity and the poromechanics of a cell cluster. Specifically, we refer to a cluster of closely packed cells, whose mechanics is governed by a polymer network of cytoskeletal filaments joined by anchoring junctions, modeled through compressible hyperelasticity. The cluster is saturated with a solution of water and ions. We account for water and ion transport in the intercellular spaces, between cells through gap junctions, and across cell membranes through aquaporins and ion channels. Water fluxes result from the contributions due to osmosis, electro-osmosis, and water pressure, while ion fluxes encompass electro-diffusive and convective terms. We consider both the cases of permeable and impermeable cluster boundary, the latter simulating the presence of sealing tight junctions. We solve the coupled governing equations for a one-dimensional axisymmetric benchmark through finite elements, thus determining the spatiotemporal evolution of the intracellular and extracellular ion concentrations, setting the membrane potential, and water concentrations, establishing the cluster deformation. When suitably complemented with genetic, biochemical, and growth dynamics, we expect this model to become a useful instrument for investigating specific aspects of developmental mechanobioelectricity.

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“…The need to coordinate molecular processes with cell shape changes and growth is a general problem beyond polarization. In this sense, mechanical feedbacks can provide important information to control morphogenesis and homeostasis in a variety of organisms [3,[86][87][88][89][90]. Identifying the molecular mechanisms enabling this coordination at different scales and in different organisms will contribute substantially to our understanding of cell dynamics.…”

Section: Plos Computational Biologymentioning

confidence: 99%

Coordinating cell polarization and morphogenesis through mechanical feedback

et al. 2021

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Many cellular processes require cell polarization to be maintained as the cell changes shape, grows or moves. Without feedback mechanisms relaying information about cell shape to the polarity molecular machinery, the coordination between cell polarization and morphogenesis, movement or growth would not be possible. Here we theoretically and computationally study the role of a genetically-encoded mechanical feedback (in the Cell Wall Integrity pathway) as a potential coordination mechanism between cell morphogenesis and polarity during budding yeast mating projection growth. We developed a coarse-grained continuum description of the coupled dynamics of cell polarization and morphogenesis as well as 3D stochastic simulations of the molecular polarization machinery in the evolving cell shape. Both theoretical approaches show that in the absence of mechanical feedback (or in the presence of weak feedback), cell polarity cannot be maintained at the projection tip during growth, with the polarization cap wandering off the projection tip, arresting morphogenesis. In contrast, for mechanical feedback strengths above a threshold, cells can robustly maintain cell polarization at the tip and simultaneously sustain mating projection growth. These results indicate that the mechanical feedback encoded in the Cell Wall Integrity pathway can provide important positional information to the molecular machinery in the cell, thereby enabling the coordination of cell polarization and morphogenesis.

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On the coupling of mechanics with bioelectricity and its role in morphogenesis

Cited by 16 publications

References 57 publications

Finite Element Modelling of a Cellular Electric Microenvironment

Finite Element Modelling of a Cellular Electric Microenvironment

Modeling the mechanobioelectricity of cell clusters

Coordinating cell polarization and morphogenesis through mechanical feedback

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