Mechanotransduction Processes Research Articles

Peripheral Mechanobiology of Touch-Studies on Vertebrate Cutaneous Sensory Corpuscles.

The vertebrate skin contains sensory corpuscles that are receptors for different qualities of mechanosensitivity like light brush, touch, pressure, stretch or vibration. These specialized sensory organs are linked anatomically and functionally to mechanosensory neurons, which function as low-threshold mechanoreceptors connected to peripheral skin through Aβ nerve fibers. Furthermore, low-threshold mechanoreceptors associated with Aδ and C nerve fibers have been identified in hairy skin. The process of mechanotransduction requires the conversion of a mechanical stimulus into electrical signals (action potentials) through the activation of mechanosensible ion channels present both in the axon and the periaxonal cells of sensory corpuscles (i.e., Schwann-, endoneurial- and perineurial-related cells). Most of those putative ion channels belong to the degenerin/epithelial sodium channel (especially the family of acid-sensing ion channels), the transient receptor potential channel superfamilies, and the Piezo family. This review updates the current data about the occurrence and distribution of putative mechanosensitive ion channels in cutaneous mechanoreceptors including primary sensory neurons and sensory corpuscles.

Effects of Matrix Stiffness on the Differentiation of Multipotent Stem Cells.

Differentiation of stem cells, a crucial step in the process of tissue development, repair and regeneration, can be regulated by a variety of mechanical factors such as the stiffness of extracellular matrix. In this review article, the effects of stiffness on the differentiation of stem cells, including bone marrow-derived stem cells, adipose-derived stem cells and neural stem cells, are briefly summarized. Compared to two-dimensional (2D) surfaces, three-dimensional (3D) hydrogel systems better resemble the native environment in the body. Hence, the studies which explore the effects of stiffness on stem cell differentiation in 3D environments are specifically introduced. Integrin is a well-known transmembrane molecule, which plays an important role in the mechanotransduction process. In this review, several integrin-associated signaling molecules, including caveolin, piezo and Yes-associated protein (YAP), are also introduced. In addition, as stiffness-mediated cell differentiation may be affected by other factors, the combined effects of matrix stiffness and viscoelasticity, surface topography, chemical composition, and external mechanical stimuli on cell differentiation are also summarized.

Crucial Role of Lamin A/C in the Migration and Differentiation of MSCs in Bone.

Lamin A/C, intermediate filament proteins from the nuclear lamina encoded by the LMNA gene, play a central role in mediating the mechanosignaling of cytoskeletal forces into nucleus. In fact, this mechanotransduction process is essential to ensure the proper functioning of other tasks also mediated by lamin A/C: the structural support of the nucleus and the regulation of gene expression. In this way, lamin A/C is fundamental for the migration and differentiation of mesenchymal stem cells (MSCs), the progenitors of osteoblasts, thus affecting bone homeostasis. Bone formation is a complex process regulated by chemical and mechanical cues, coming from the surrounding extracellular matrix. MSCs respond to signals modulating the expression levels of lamin A/C, and therefore, adapting their nuclear shape and stiffness. To promote cell migration, MSCs need soft nuclei with low lamin A content. Conversely, during osteogenic differentiation, lamin A/C levels are known to be increased. Several LMNA mutations present a negative impact in the migration and osteogenesis of MSCs, affecting bone tissue homeostasis and leading to pathological conditions. This review aims to describe these concepts by discussing the latest state-of-the-art in this exciting area, focusing on the relationship between lamin A/C in MSCs’ function and bone tissue from both, health and pathological points of view.

Characterization of arterial flow mediated dilation via a physics-based model

In this paper, a physics-based mathematical model is developed to describe the transient behavior of the brachial artery during the Flow Mediated Dilation (FMD) test. The change of the artery's diameter was collected for 7 cases via in vivo, non-invasive ultrasound imaging. A theoretical model was developed to capture the response of the blood vessel to the change of the blood flow, in which the vessel's compliance is modeled as a function of the wall shear stress (WSS). The theory precisely captures the key feature of the mechanotransduction process, which a conventional viscoelastic model fails to describe. Three characteristic dimensionless parameters were obtained from the model, quantifying the physical state of the artery and related to the cardiovascular health. The transient physics, manifested in the two-way (where both arterial compliance and blood flow conditions affect each other) Fluid-Structure Interaction (FSI) process, present an interesting opportunity to explore the nature of living materials making up the arterial walls, which would in turn lead to a better understanding and therefore detection of the onset of some forms of cardiovascular diseases (CVD).

αvβ3 integrin expression increases elasticity in human melanoma cells

Living cells interact with the extracellular matrix (ECM) transducing biochemical signals into mechanical cues and vice versa. Thanks to this mechano-transduction process, cells modify their internal organization and upregulate their physiological functions differently. In this complex mechanism integrins play a fundamental role, connecting the extracellular matrix with the cytoskeleton. Cytoskeletal rearrangements, such as the increase of the overall contractility, impact cell mechanical properties, the entire cell stiffness, and cell deformability. How cell mechanics is influenced via different integrins and their interaction with ECM in health and disease is still unclear. Here, we investigated the influence of αvβ3 integrin expression on the mechanics of human melanoma M21 cells using atomic force microscopy and micro-constriction. Evidence is provided that (i) αvβ3 integrin expression in human melanoma cells increases cell stiffness in both adherent and non-adherent conditions; (ii) replacing αvβ3 with αIIbβ3 integrin in melanoma cells, cell stiffness is increased under adherent, while decreased under non-adherent conditions; (iii) αvβ3 integrin cell stiffening is also maintained when cells adhere to fibronectin, but this phenomenon does not strongly depend on the fibronectin concentration. In all, this study sheds light on the role of αvβ3 in regulating cellular mechanics.

Structure and Mechanogating of the Mechanosensitive PIEZO Channel

The evolutionarily conserved PIEZO family of proteins, including PIEZO1 and PIEZO2, forms the long-sought bona fide mammalian mechanosensitive cation channel, and plays critical roles in various mechanotransduction processes such as touch, proprioception, tactile pain, vascular development and blood pressure regulation. Taking a multidisciplinary approach combining protein engineering and purification, cryo-EM, electrophysiology and drug screening, we have determined the three-bladed, propeller-like trimeric structures of both PIEZO1 and PIEZO2 that comprises 114 transmembrane helices (38 per protomer). Transmembrane helices 1-36 (TM1-36) are folded into nine tandem transmembrane helical units (THU) of four TMs each to form the unusual non-planar blades. The three blades are collectively curved into a nano-bowl shape of 28-nm diameter and 10-nm depth, with an extracellular cap-like structure embedded in the centre and a 9-nm-long intracellular beam connecting to the central pore. TM38 and the C-terminal domain are surrounded with the anchor domain and TM37, and enclose the central pore with both transmembrane and cytoplasmic constriction sites. Structural comparison between PIEZO1 and PIEZO2 has revealed that the transmembrane constriction site might act as a transmembrane gate. Structural and functional analyses have suggested that the PIEZO channel might employ the top cap to control the transmembrane gate, while the blade-beam might function as a lever-like apparatus to allosterically control the putative cytosolic gate, indicating a dual-gating mechanism. Together, our studies provide insights into the structure and mechanogating mechanism of PIEZO channels.

Viscoelastic Mechanical Models of the LINC Complex

Cell adhesion, cell spreading and cell-cell communications depend on mechanotransduction processes. Mechanical signals are sensed by integrins on the plasma membrane and then cross the cytoplasm through mechantransduction pathways ultimately reaching chromosomes, eliciting changes in gene expressions. One of the critical parts of these mechanochemical pathways is the linker of the nucleoskeleton and cytoskeleton, known as the LINC complexes. LINC complexes comprise two main proteins, SUN and KASH (a peptide at the tip of Nesprins). The stable connection between SUN and KASH is necessary for cell functioning. In this study, we modeled LINC complex with the combination of different viscoelastic compartments based closely on our molecular dynamic simulations. We divided the LINC complex to different sections connected by spring-dashpot viscoelastic models. We use these viscoelastic models to incorporate and interrogate the contribution of different components of the LINC complex. For example, we investigated the threshholding effect of disulfide bond between C6862 residue of KASH2 and C536 of SUN2 domain on the force transmission, which, as we previously showed, plays a critical role in LINC complex function. Here, we tuned model parameters to model truncated KASH and cysteine-mutated LINC based on our previous molecular dynamic simulations. Our proposed viscoelastic model allows us to investigate the effect of different factors such as proposed mutations on the signal transmission through LINC with tuning model parameters. Together with our all-atom molecular dynamics models, these viscoelastic models can help us gain a better understanding of the LINC complex in the context of other mechanochemical elements of mechanotransduction pathway.

Domain-Dependent Force Selectivity in the Mechanosensitive Ion Channel Piezo1

Piezo1 is a mechanosensitive ion channel noted for its exceptional complexity and involvement in force sensing in a broad range of tissues, including cartilage, bone, skin, blood vessels and lymph nodes. While cell-specific splice variants have been reported in the closely related Piezo2 channel, and various membrane proteins and lipids have been demonstrated to modulate the mechanotransduction process, it is less clear how Piezo1 attunes itself to tissue microenvironments with greatly divergent force profiles. Here, we describe chimeric cpGFP/Piezo1 probes that selectively respond to shear stress with a strong and irreversible increase in fluorescence intensity. Probe sensitivity is correlated with the presence an actin cytoskeleton, the inhibition of which dampens but does not eliminate the signal. The reporters retain functional pores and allow cation entry in response to the Piezo1 agonist Yoda1, as well as poking with a glass probe and exposure to a hypotonic environment, but these stimuli do not trigger a fluorescent response. Similarly, no shear response is provided by cpGFP inserted into other regions of Piezo1, as well as non-mechanosensitive reporters (Lck-cpGFP and the voltage-sensitive reporter ASAP1). Evolutionary analysis of Piezo1 sequences show that different clusters of conserved and co-mutating residues exist in the blade region, suggesting that multiple allosteric pathways may be responsible for conveying different types of mechanical stress to the pore. We propose that other sets of Piezo1 insertions can be used to determine the function of these clusters.

Model of the Nerve Impulse with Account of Mechanosensory Processes: Stationary Solutions.

Mechanotransduction refers to a physiological process by which mechanical forces, such as pressures exerted by ionized fluids on cell membranes and tissues, can trigger excitations of electrical natures that play important role in the control of various sensory (i.e. stimuli-responsive) organs and homeostasis of living organisms. In this work, the influence of mechanotransduction processes on the generic mechanism of the action potential is investigated analytically, by considering a mathematical model that consists of two coupled nonlinear partial differential equations. One of these two equations is the Korteweg-de Vries equation governing the spatio-temporal evolution of the density difference between intracellular and extracellular fluids across the nerve membrane, and the other is Hodgkin-Huxley cable equation for the transmembrane voltage with a self-regulatory (i.e. diode-type) membrane capacitance. The self-regulatory feature here refers to the assumption that membrane capacitance varies with the difference in density of ion-carrying intracellular and extracellular fluids, thus ensuring an electromechanical feedback mechanism and consequently an effective coupling of the two nonlinear equations. The exact one-soliton solution to the density-difference equation is obtained in terms of a pulse excitation. With the help of this exact pulse solution the Hodgkin-Huxley cable equation is shown to transform, in steady state, to a linear eigenvalue problem some bound states of which can be obtained exactly. Few of such bound-state solutions are found analytically.

Probing Multidimensional Mechanical Phenotyping of Intracellular Structures by Viscoelastic Spectroscopy.

Mechanical phenotyping of complex cellular structures gives insight into the process and function of mechanotransduction in biological systems. Several methods have been developed to characterize intracellular elastic moduli, while direct viscoelastic characterization of intracellular structures is still challenging. Here, we develop a needle tip viscoelastic spectroscopy method to probe multidimensional mechanical phenotyping of intracellular structures during a mini-invasive penetrating process. Viscoelastic spectroscopy is determined by magnetically driven resonant vibration (about 15 kHz) with a tiny amplitude. It not only detects the unique dynamic stiffness, damping, and loss tangent of the cell membrane-cytoskeleton and nucleus-nuclear lamina but also bridges viscoelastic parameters between the mitotic phase and interphase. Self-defined dynamic mechanical ratios of these two phases can identify two malignant cervical cancer cell lines (HeLa-HPV18+, SiHa-HPV16+) whose membrane or nucleus elastic moduli are indistinguishable. This technique provides a quantitative method for studying mechanosensation, mechanotransduction, and mechanoresponse of intracellular structures from a dynamic mechanical perspective. This technique has the potential to become a reliable quantitative measurement method for dynamic mechanical studies of intracellular structures.

A Micropatterning Strategy to Study Nuclear Mechanotransduction in Cells.

Micropatterning techniques have been widely used in biology, particularly in studies involving cell adhesion and proliferation on different substrates. Cell micropatterning approaches are also increasingly employed as in vitro tools to investigate intracellular mechanotransduction processes. In this report, we examined how modulating cellular shapes on two-dimensional rectangular fibronectin micropatterns of different widths influences nuclear mechanotransduction mediated by emerin, a nuclear envelope protein implicated in Emery–Dreifuss muscular dystrophy (EDMD). Fibronectin microcontact printing was tested onto glass coverslips functionalized with three different silane reagents (hexamethyldisilazane (HMDS), (3-Aminopropyl)triethoxysilane (APTES) and (3-Glycidyloxypropyl)trimethoxysilane (GPTMS)) using a vapor-phase deposition method. We observed that HMDS provides the most reliable printing surface for cell micropatterning, notably because it forms a hydrophobic organosilane monolayer that favors the retainment of surface antifouling agents on the coverslips. We showed that, under specific mechanical cues, emerin-null human skin fibroblasts display a significantly more deformed nucleus than skin fibroblasts expressing wild type emerin, indicating that emerin plays a crucial role in nuclear adaptability to mechanical stresses. We further showed that proper nuclear responses to forces involve a significant relocation of emerin from the inner nuclear envelope towards the outer nuclear envelope and the endoplasmic reticulum membrane network. Cell micropatterning by fibronectin microcontact printing directly on HMDS-treated glass represents a simple approach to apply steady-state biophysical cues to cells and study their specific mechanobiology responses in vitro.

Fabrication and Implementation of a Reference-Free Traction Force Microscopy Platform.

Quantifying cell-induced material deformation provides useful information concerning how cells sense and respond to the physical properties of their microenvironment. While many approaches exist for measuring cell-induced material strain, here we provide a methodology for monitoring strain with sub-micron resolution in a reference-free manner. Using a two-photon activated photolithographic patterning process, we demonstrate how to generate mechanically and bio-actively tunable synthetic substrates containing embedded arrays of fluorescent fiducial markers to easily measure three-dimensional (3D) material deformation profiles in response to surface tractions. Using these substrates, cell tension profiles can be mapped using a single 3D image stack of a cell of interest. Our goal with this methodology is to make traction force microscopy a more accessible and easier to implement tool for researchers studying cellular mechanotransduction processes, especially newcomers to the field.

Tissue Regeneration from Mechanical Stretching of Cell-Cell Adhesion.

Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. This mechanochemical coupling in cell-cell adhesion is required for a large number of cell behaviors, and perturbations of the cell-cell adhesion structure or related mechanotransduction pathways can lead to critical pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been a widely used method to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. These studies aimed to reveal the biophysical processes governing cell proliferation, wound healing, gene expression regulation, and cell differentiation in various tissues, including cardiac, muscle, vascular, and bone. This review explores techniques in mechanical stretching in two-dimensional settings with different stretching regimens on different cell types. The mechanotransduction responses from these different cell types will be discussed with an emphasis on their biophysical transformations during mechanical stretching and the cross talk between the cell-cell and cell-ECM adhesion complexes. Therapeutic aspects of mechanical stretching are reviewed considering these cellular responses after the application of mechanical forces, with a focus on wound healing and tissue regeneration. Impact Statement Mechanical stretching has been proposed as a therapeutic option for tissue regeneration and wound healing. It has been accepted that mechanotransduction processes elicited by mechanical stretching govern cellular response and behavior, and these studies have predominantly focused on the cell-extracellular matrix (ECM) sites. This review serves the mechanobiology community by shifting the focus of mechanical stretching effects from cell-ECM adhesions to the less examined cell-cell adhesions, which we believe play an equally important role in orchestrating the response pathways.

Studying the Response of Aortic Endothelial Cells under Pulsatile Flow Using a Compact Microfluidic System.

We describe a piezoelectric pumping system for studying the mechanobiology of human aortic endothelial cells (HAECs) under pulsatile flow in microfluidic structures. The system takes advantage of commercially available components, including pumps, flow sensors, and microfluidic channels, which can be easily integrated, programmed, and operated by cellular biologists. Proof-of-concept experiments were performed to elucidate the complex mechanotransduction processes of endothelial cells to pulsatile flow. In particular, we investigated the effect of atheroprone and atheroprotective pulsatile shear stress on endothelial cytoskeleton remodeling and distribution of β-catenin, as well as nuclear shape and size. The system is simple to operate, relatively inexpensive, portable, and controllable, providing opportunities for studying the mechanobiology of endothelial cells using microfluidic technologies.

A biomaterials approach to Schwann cell development in neural tissue engineering.

Schwann cells, in addition to forming myelin sheaths, have pivotal roles in regeneration of injured axons in the peripheral nervous system such as producing a natural permissive conduit between distal and proximal stumps and secreting nerve growth factors. Due to the atrophy and senescence of Schwann cells in long nerve gap, and the need to ensure the presence of nerve growth factors and basal lamina tubes for axon regeneration in a critical time, injection of Schwann cells with the aid of an engineered conduit seems to be an effective approach to induce axon regrowth. Stem cells with high differentiation and proliferation capability can provide an adequate number of Schwann cells in healthy state for regeneration purposes. Guidance of stem cells differentiation into desired lineages, control of implanted Schwann cells fate, maintenance of nerve growth factors expression, and guidance of axon regrowth are possible with the aid of biomaterials with appropriate chemical, physical, and mechanical properties. Biomaterials' surface chemistry and biomolecules interacting with cells' receptors initiate specific intracellular signaling cascades and direct cells fate. In addition, biomaterials' surface topography in association with cells contact area, focal adhesion, and cytoskeletal remodeling by mechanotransduction process influences cells behavior and induces specific differentiation. The main objective of this review is to investigate the chemical, topographical, and mechanical properties of biomaterials which influence the fate of Schwann cells and the nerve regeneration process.

Substrate Compliance Directs the Osteogenic Lineages of Stem Cells from the Human Apical Papilla via the Processes of Mechanosensing and Mechanotransduction.

It is well recognized that the interaction between stem cells and their physical microenvironment plays a fundamental role in controlling cell behaviors and directing lineage commitment, which eventually determines cell fate. Any change in the physical characteristics of the extracellular matrix in terms of topography, geometry, and stiffness has a strong effect on this interaction. Nevertheless, the precise biomechanism that regulates the responses of stem cells to the biophysical properties of substrates is not fully understood. In this study, we generated a series of polydimethylsiloxane (PDMS) substrates with different stiffness properties and explored the whole process involved in the determination of osteogenic lineage in stem cells from the human apical papilla (hSCAPs) in response to substrate stiffness. We first found that the hSCAPs responded to different substrate stiffnesses by changing their cell morphologies and cytoskeletons (via changes in α-tubulin and β-tubulin in microtubules and F-actin in microfilaments). We then found that the hSCAPs secreted more fibronectin in response to the stiffer substrates. We next found that fibronectin interacted with focal adhesion kinase (FAK) and paxillin in the FA plaques, and moreover, the expressions of FAK and paxillin were enhanced as the substrate stiffness increased. We further found that FAK and paxillin directly interacted with β-catenin. Furthermore, the accumulation of β-catenin in the nuclear region was strengthened as the substrate stiffness increased. We finally detected the changes of Lef-1 and TCF-1 in osteogenic-induced hSCAPs and found that their expressions were enhanced as the substrate stiffness increased. Lef-1 and TCF-1, as the transcriptional factors in the nucleus, potentially bound to the promoter region of Runx2 and might ultimately determine the osteogenic lineage in hSCAPs. These results indicate the important effect of stiffness in the microenvironment on the osteogenic lineage of hSCAPs and increase the understanding of the biomechanisms involved in the molecular signal cascade during mechanosensing, mechanotransduction, and stem cell differentiation, which will be useful in the biological fields of cell-matrix/cell-cell interactions and tissue engineering/regenerative medicine.

Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation.

The nucleus houses, organizes, and protects chromatin to ensure genome integrity and proper gene expression, but how the nucleus adapts mechanically to changes in the extracellular environment is poorly understood. Recent studies have revealed that extracellular physical stresses induce chromatin compaction via mechanotransductive processes. We report that increased extracellular multivalent cations lead to increased heterochromatin levels through activation of mechanosensitive ion channels (MSCs), without large-scale cell stretching. In cells with perturbed chromatin or lamins, this increase in heterochromatin suppresses nuclear blebbing associated with nuclear rupture and DNA damage. Through micromanipulation force measurements, we show that this increase in heterochromatin increases chromatin-based nuclear rigidity, which protects nuclear morphology and function. In addition, transduction of elevated extracellular cations rescues nuclear morphology in model and patient cells of human diseases, including progeria and the breast cancer model cell line MDA-MB-231. We conclude that nuclear mechanics, morphology, and function can be modulated by cell sensing of the extracellular environment through MSCs and consequent changes to histone modification state and chromatin-based nuclear rigidity.

Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation.

The nucleus houses, organizes, and protects chromatin to ensure genome integrity and proper gene expression, but how the nucleus adapts mechanically to changes in the extracellular environment is poorly understood. Recent studies have revealed that extracellular physical stresses induce chromatin compaction via mechanotransductive processes. We report that increased extracellular multivalent cations lead to increased heterochromatin levels through activation of mechanosensitive ion channels, without large-scale cell stretching. In cells with perturbed chromatin or lamins, this increase in heterochromatin suppresses nuclear blebbing associated with nuclear rupture and DNA damage. Through micromanipulation force measurements, we show that this increase in heterochromatin increases chromatin-based nuclear rigidity, which protects nuclear morphology and function. In addition, transduction of elevated extracellular cations rescues nuclear morphology in model and patient cells of human diseases, including progeria and the breast cancer model cell line MDA-MB-231. We conclude that nuclear mechanics, morphology, and function can be modulated by cell sensing of the extracellular environment through mechanosensitive ion channels and consequent changes to histone modification state and chromatin-based nuclear rigidity.

The role of three-dimensionality and alveolar pressure in the distribution and amplification of alveolar stresses

Alveolar stresses are fundamental to enable the respiration process in mammalians and have recently gained increasing attention due to their mechanobiological role in the pathogenesis and development of respiratory diseases. Despite the fundamental physiological role of stresses in the alveolar wall, the determination of alveolar stresses remains challenging, and our current knowledge is largely drawn from 2D studies that idealize the alveolar septal wall as a spring or a planar continuum. Here we study the 3D stress distribution in alveolar walls of normal lungs by combining ex-vivo micro-computed tomography and 3D finite-element analysis. Our results show that alveolar walls are subject to a fully 3D state of stresses rather than to a pure axial stress state. To understand the contributions of the different components and deformation modes, we decompose the stress tensor field into hydrostatic and deviatoric components, which are associated with isotropic and distortional stresses, respectively. Stress concentrations arise in localized regions of the alveolar microstructure, with magnitudes that can be up to 27 times the applied alveolar pressure. Interestingly, we show that the stress amplification factor strongly depends on the level of alveolar pressure, i.e, stresses do not scale proportional to the applied alveolar pressure. In addition, we show that 2D techniques to assess alveolar stresses consistently overestimate the stress magnitude in alveolar walls, particularly for lungs under high transpulmonary pressure. These findings take particular relevance in the study of stress-induced remodeling of the emphysematous lung and in ventilator-induced lung injury, where the relation between transpulmonary pressure and alveolar wall stress is key to understand mechanotransduction processes in pneumocytes.

"Force-From-Lipids" mechanosensation in Corynebacterium glutamicum.

Since the mechanosensitive channel MscCG has been identified as the major glutamate efflux system in Corynebacterium glutamicum, studies of mechanotransduction processes in this bacterium have helped to unpuzzle a long-unresolved mystery of glutamate efflux that has been utilised for industrial monosodium glutamate production. The patch clamp recording from C. glutamicum giant spheroplasts revealed the existence of three types of mechanosensitive (MS) channels in the cell membrane of this bacterium. The experiments demonstrated that the MS channels could be activated by membrane tension, indicating that the channel gating by mechanical force followed the "Force-From-Lipids (FFL)" principle characteristic of ion channels inherently sensitive to transbilayer pressure profile changes in the mechanically stressed membrane bilayer. Mechanical properties of the C. glutamicum membrane are characteristics of very soft membranes, which in the C. glutamicum membrane are due to negatively charged lipids as its exclusive constituents. Given that membrane lipids are significantly altered during the fermentation process in the monosodium glutamate production, MS channels seem to respond to changes in force transmission through the membrane bilayer due to membrane lipid dynamics. In this review, we describe the recent results describing corynebacterial FFL-dependent mechanosensation originating from the particular lipid composition of the C. glutamicum membrane and unique structure of MscCG-type channels.