Microenvironment and cell mechanics

Microenvironment contains biophysical and biochemical elements to maintain survival,growth,proliferation,and differentiation of cells.Any change can lead to cell response to the mechanical forces,which can be described by elasticity.It is an indicator of a cell’s state since it plays an important role in many cellular processes.In many cases,cell elasticity is measured by using discontinuous manner,which may not allow elucidating real-time activity of individual live cells in physiological condition or cell response against microenvironmental changes.I argue that measuring cell elasticity using continuously repetitive nanoindentation technique is important that should be considered.As an example,I discuss mechanics of human embryonic kidney(HEK)cells in various conditions.In resting cells,there is an activity of the cytoskeleton whose oscillation amplitude is strongly affected by the intracellular calcium,and the collective activity of myosin motor proteins induces elasticity oscillation.Experimental results also reveal that actin cytoskeleton and cell membrane determine cell mechanics.

F-Actin reassembly during focal adhesion impacts single cell mechanics and nanoscale membrane structure

Focal adhesions play an important role in cell spreading,migration,and overall mechanical integrity.The relationship of cell structural and mechanical properties was investigated in the context of focal adhesion processes.Combined atomic force microscopy(AFM) and laser scanning confocal microscopy(LSCM) was utilized to measure single cell mechanics,in correlation with cellular morphology and membrane structures at a nanometer scale.Characteristic stages of focal adhesion were verified via confocal fluorescent studies,which confirmed three representative F-actin assemblies,actin dot,filaments network,and long and aligned fibrous bundles at cytoskeleton.Force-deformation profiles of living cells were measured at the single cell level,and displayed as a function of height deformation,relative height deformation and relative volume deformation.As focal adhesion progresses,single cell compression profiles indicate that both membrane and cytoskeleton stiffen,while spreading increases especially from focal complex to focal adhesion.Correspondingly,AFM imaging reveals morphological geometries of spherical cap,spreading with polygon boundaries,and elongated or polarized spreading.Membrane features are dominated by protrusions of 41-207 nm tall,short rods with 1-6 μm in length and 10.2-80.0 nm in height,and long fibrous features of 31-246 nm tall,respectively.The protrusion is attributed to local membrane folding,and the rod and fibrous features are consistent with bilayer decorating over the F-actin assemblies.Taken collectively,the reassembly of F-actin during focal adhesion formation is most likely responsible for the changes in cellular mechanics,spreading morphology,and membrane structural features.

Mechanopathology of red blood cell diseases—Why mechanics matters

During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular structures.These alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape,deformability and adhesion.As such,knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ones.Here,we will present biomechanistic insights into red blood cell related diseases that manifest mechanical property changes and how they directly contribute to the pathophysiology of diseases.By conducting cell and molecular mechanics studies,not only can we elucidate changes in the structure-property-function relationship of diseased cells,we can also exploit the new knowledge gained to develop biomechanics based devices that may better detect and diagnose these diseases as well as help identify important biomechanical targets for possible therapeutic interventions.

Cell mechanics and energetic costs of collective cell migration under confined microchannels

Mechanical force between cells relates to many biological processes of cell development.The cellular collective migration comes from cell-cell cooperation,and studying the intercellular mechanical properties helps elucidate collective cell migration.Herein,we studied cell-cell junctions,intercellular tensile force and the related cellular energetic costs in confined microchannels.Using the intercellular force sensor,we found that cells adapt to different confinement environments by regulating intercellular force,and thereby the relationship between collective cell migration and cell-cell junction were verified.Through the observation of cell orientation,actomyosin contractility,energetic costs,and glucose uptake,we can make a reasonable explanation of cell-force driven migration in different confined environments.Under highly confined conditions,the intercellular force and energetic costs are greater,and the cell orientation is more orderly.The collective migration behavior in confined spaces is closely related to the intercellular force and energetic costs,which is helpful to understand the collective migration behaviors in various confined spaces.

Mechanics of mechanosensitivity of cell

Focal adhesions(FAs) are large,multiprotein complexs that provides linkers between cytoskeleton to the extracellular matrix(ECM).Cells sense and respond to forces through FAs to regulate a broad range of processes,such as cell growth,migration,differentiation

Mechanics of mechanosensitivity of cell

Cells sense and respond to forces and extracellular environment through FAs to regulate a broad range of processes, such as cell growth,migration,differentiation and apoptosis. Currently,the underlying mechanisms of the force

Probing the mechanosensitivity in cell adhesion and migration: Experiments and modeling

Cell adhesion and migration are basic physiolog- ical processes in living organisms. Cells can actively probe their mechanical micro-environment and respond to the ex- ternal stimuli through cell adhesion. Cells need to move to the targeting place to perform function via cell migration. For adherent cells, cell migration is mediated by cell-matrix adhesion and cell-cell adhesion. Experimental approaches, especially at early stage of investigation, are indispensable to studies of cell mechanics when even qualitative behaviors of cell as well as fundamental factors in cell behaviors are unclear. Currently, there is increasingly accumulation of ex- perimental data of measurement, thus a quantitative formula- tion of cell behaviors and the relationship among these fun- damental factors are highly needed. This quantitative under- standing should be crucial to tissue engineering and biomed- ical engineering when people want to accurately regulate or control cell behaviors from single cell level to tissue level. In this review, we will elaborate recent advances in the ex- perimental and theoretical studies on cell adhesion and mi- gration, with particular focuses laid on recent advances in experimental techniques and theoretical modeling, through which challenging problems in the cell mechanics are sug- gested.

OPTICALLY TRACKING THE MOTION OF MICROBEADS TO STUDY PHYSICAL BEHAVIORS OF THE LIVING CELL IN RESPONSE TO TRANSIENT STRETCH OR COMPRESSION

Optical magnetic twisting cytometry and traction force microscopy are two advanced cell mechanics research tools that employ optical methods to track the motion of microbeads that are either bound to the surface or embedded in the substrate underneath the cell.The former measures rheological properties of the cell such as cell stiffness,and the latter measures cell traction force dynamics.Here we describe the principles of these two cell mechanics research tools and an example of using them to study physical behaviors of the living cell in response to transient stretch or compression.We demonstrate that,when subjected to a stretch
unstretch manipulation,both the stiffness and traction force of adherent cells promptly reduced,and then gradually recover up to the level prior to the stretch.Immunofluorescent staining and Western blotting results indicate that the actin cytoskeleton of the cells underwent a corresponding disruption and reassembly process almost in step with the changes of cell mechanics.Interestingly,when subjected to compression,the cells did not show such particular behaviors.Taken together,we conclude that adherent cells are very sensitive to the transient stretch but not transient compression,and the stretch-induced cell response is due to the dynamics of actin polymerization.

Fluid and Osmotic Pressure Balance and Volume Stabilization in Cells Dedicated to Professor Karl Stark Pister for his 95th birthday

A fundamental problem for cells with their fragile membranes is the control of their volume.The primordial solution to this problem is the active transport of ions across the cell membrane to modulate the intracellular osmotic pressure.In this work,a theoretical model of the cellular pump-leak mechanism is proposed within the general framework of linear nonequilibrium thermodynamics.The model is expressed with phenomenological equations that describe passive and active ionic transport across cell membranes,supplemented by an equation for the membrane potential that accounts for the electrogenicity of the ionic pumps.For active ionic transport,the model predicts that the intracellular fluid pressure will be balanced by the osmotic pressure and a new pressure component that arises from the active ionic fluxes.A model for the pump-leak mechanism in an idealized human cell is introduced to demonstrate the applicability of the proposed theory.

Precise robust motion control of cell puncture mechanism driven by piezoelectric actuators with fractional-order nonsingular terminal slidingmode control

A novel robust controller is proposed in this study to realize the precise motion control of a cell puncture mechanism(CPM)driven by piezoelectric ceramics(PEAs).The entire dynamic model of CPM is constructed based on the Bouc–Wen model,and the nonlinear part of the dynamic model is optimized locally to facilitate the construction of a robust controller.A model-based,nonlinear robust controller is constructed using time-delay estimation(TDE)and fractional-order nonsingular terminal sliding mode(FONTSM).The proposed controller does not require prior knowledge of unknown disturbances due to its real-time online estimation and compensation of unknown terms by using the TDE technology.The controller also has finite-time convergence and high-precision trajectory tracking capabilities due to FONTSM manifold and fast terminal sliding mode-type reaching law.The stability of the closed-loop system is proved by Lyapunov stability theory.Computer simulation and hardware-in-loop simulation experiments of CPM verify that the proposed controller outperforms traditional terminal sliding mode controllers,such as the integer-order or model-free controller.The proposed controller can also continuously output without chattering and has high control accuracy.Zebrafish embryo is used as a verification target to complete the cell puncture experiment.From the engineering application perspective,the proposed control strategy can be effectively applied in a PEA-driven CPM.

Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting

Pediatric neuroblastomas(NBs)are heterogeneous,aggressive,therapy-resistant embryonal tumours that originate from cells of neural crest(NC)origin and in particular neuroblasts committed to the sympathoadrenal progenitor cell lineage.Therapeutic resistance,post-therapeutic relapse and subsequent metastatic NB progression are driven primarily by cancer stem cell(CSC)-like subpopulations,which through their self-renewing capacity,intermittent and slow cell cycles,drug-resistant and reversibly adaptive plastic phenotypes,represent the most important obstacle to improving therapeutic outcomes in unfavourable NBs.In this review,dedicated to NB CSCs and the prospects for their therapeutic eradication,we initiate with brief descriptions of the unique transient vertebrate embryonic NC structure and salient molecular protagonists involved NC induction,specification,epithelial to mesenchymal transition and migratory behaviour,in order to familiarise the reader with the embryonic cellular and molecular origins and background to NB.We follow this by introducing NB and the potential NC-derived stem/progenitor cell origins of NBs,before providing a comprehensive review of the salient molecules,signalling pathways,mechanisms,tumour microenvironmental and therapeutic conditions involved in promoting,selecting and maintaining NB CSC subpopulations,and that underpin their therapy-resistant,self-renewing metastatic behaviour.Finally,we review potential therapeutic strategies and future prospects for targeting and eradication of these bastions of NB therapeutic resistance,post-therapeutic relapse and metastatic progression.

Mechanochemical mechanisms of embryonic stem cell pluripotency and differentiation

Embryonic stem (ES) cell biology is attracting much attention in cell biology because of their pluripotent behaviors and potential therapeutic applications. However,what maintains ES cell pluripotency and what triggers ES cell

Multi-effects and Mechanism of Broad Beau M_1 Root-tip Cells Implanted by Low Energy N^+ Beam

Broad beans were divided into six groups and implanted with N+ beam of 30 KeV, 8 × 1016/cm2 per time for various radiating times respectively. Besides the statistics of its vigor of germination, the M1 root-tip cells of these broad beans were systematically analyzed on their changes in mitotic percentage, morphology and behavior of chromosomes, along with the structure o f cytoskeletons, including microtubule and intermediate filament. Based on all results of these studies, our opinions have been expressed in the report on the mechanism of low-energy N+ beams effecting on higher dicotyledons such as broad beau.

A STUDY OF THE FORMATION OF LIVER METASTASIS AND ITS MECHANISM USING THE INTRASPLENIC INOCULATION OF CANCER CELLS

In order to establish an animal model with hepatic metastasis intrasplenic inoculation of carcinoma cells from murine uterine cervical carcinoma (U14) was employed. Results showed a high incidence of hepatic metastasis could be obtained through the intrasplenic inoculation of 1 × 106 carcinoma cells. Removal of the primary carcinoma through splenec-tomy at different intervals after intrasplenic inoculation proved that the hepatic metastatic mechanism was not due to mechanical pressure but occurred spontaneously. This experimental model provides a useful means for studying the mechanism and prevention of hepatic metastasis.

Mechanics of serotonin-producing human entero-endocrine cells

The gastrointestinal(GI)tract's primary role is food digestion,relying on coordinated fluid secretion and bowel movements triggered by mechanosensation.Enteroendocrine cells(EECs)are specialized mechanosensitive cells that convert mechanical forces into electrochemical signals,culminating in serotonin release to regulate GI motility.Despite their pivotal role,knowledge of EEC mechanical properties has been lacking due to their rarity and limited accessibility.In this brief report,we present the first single-cell mechanical characterization of human ECCs isolated from healthy intestinal organoids.Using single-cell optical tweezers,we measured EEC stiffness profiles at the physiological temperature and investigated changes following tryptophan metabolism inhibition.Our findings not only shed light on EEC mechanics but also highlight the potential of adult stem cell-derived organoids for studying these elusive cells.

Role of OX40 in mechanisms of memory T cells in islet transplant tolerance

Objective To investigate the role of OX40 in the mechanisms of memory T cells in islet transplant tolerance. Methods The expression of OX40 on native, like memory and memory CD8 + T cells was detected by RT - PCR. Splenic T ceels from B6 mice were injected into Rag - / - mice via the tail vein,and the Rag mice were divided into three groups ( n = 8 each) :

Effect and mechanism of adrenomedullin on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury

Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-

CELL AND MOLECULAR BIOMECHANICS: PERSPECTIVES AND CHALLENGES

As an intriguing interdisciplinary research field, cell and molecular biomechanics is at the cutting edge of mechanics in general and biomechanics in particular. It has the potential to provide a quantitative understanding of how forces and deformation at tissue, cellular and molecular levels affect human health and disease. In this article, we review the recent advances in cell and molecular biomechanics, examine the available computational and experimental tools, and discuss important issues including protein deformation in mechanotransduction, cell deformation and constitutive behavior, cell adhesion and migration, and the associated models and theories. The opportunities and challenges in cell and molecular biomechanics are also discussed. We hope to provide readers a clear picture of the current status of this field, and to stimulate a broader interest in the applied mechanics community.