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.

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.

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...

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

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.

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.

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.

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.

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-

Hippo signaling:bridging the gap between cancer and neurodegenerative disorders

During development,regulation of organ size requires a balance between cell proliferation,growth and cell death.Dysregulation of these fundamental processes can cause a variety of diseases.Excessive cell proliferation results in cancer whereas excessive cell death results in neurodegenerative disorders.Many signaling pathways known-to-date have a role in growth regulation.Among them,evolutionarily conserved Hippo signaling pathway is unique as it controls both cell proliferation and cell death by a variety of mechanisms during organ sculpture and development.Neurodegeneration,a complex process of progressive death of neuronal population,results in fatal disorders with no available cure to date.During normal development,cell death is required for sculpting of an organ.However,aberrant cell death in neuronal cell population can result in neurodegenerative disorders.Hippo pathway has gathered major attention for its role in growth regulation and cancer,however,other functions like its role in neurodegeneration are also emerging rapidly.This review highlights the role of Hippo signaling in cell death and neurodegenerative diseases and provide the information on the chemical inhibitors employed to block Hippo pathway.Understanding Hippo mediated cell death mechanisms will aid in development of reliable and effective therapeutic strategies in future.

High-throughput physical phenotyping of cell differentiation

In this report,we present multiparameter deformability cytometry(m-DC),in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives.m-DC utilizes microfluidic inertial focusing and hydrodynamic stretching of single cells in conjunction with high-speed video recording to realize high-throughput characterization of over 20 different cell motion and morphology-derived parameters.Parameters extracted from videos include size,deformability,deformation kinetics,and morphology.We train support vector machines that provide evidence that these additional physical measurements improve classification of induced pluripotent stem cells,mesenchymal stem cells,neural stem cells,and their derivatives compared to size and deformability alone.In addition,we utilize visual interactive stochastic neighbor embedding to visually map the high-dimensional physical phenotypic spaces occupied by these stem cells and their progeny and the pathways traversed during differentiation.This report demonstrates the potential of m-DC for improving understanding of physical differences that arise as cells differentiate and identifying cell subpopulations in a label-free manner.Ultimately,such approaches could broaden our understanding of subtle changes in cell phenotypes and their roles in human biology.

The Possibility and Molecular Mechanisms of Cell Pyroptosis After Cerebral Ischemia

Introduction Stroke is an important disease that is prevalent worldwide [1-3].Ischemic stroke accounts for 80%of stroke cases. Currently,evidence-based effective treatments for ischemic stroke are limited,and only intravenous throm- bolysis with Alteplase (a commercially available throm- bolytic agent)within 4.5 h of stroke onset and thrombectomy and arterial thrombolysis within 6-24h of onset are effective [4,5].However,because these two treatments have strict indications and certain risks (reper- fusion injury and bleeding)[5-8],there is an urgent need to develop new treatment methods.Thus,comprehensive elucidation of the molecular mechanisms underlying ischemic brain damage and the search for key signaling pathways and protein molecules are important for guiding the clinical treatment of ischemic stroke.

Molecular mechanisms of TRAIL-induced apoptosis of cancer cells

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a recently identified member of the tumor necrosis factor (TNF) family[1]. Numerous studies indicate that TRAIL can induce apoptosis of cancer cells but not of normal cells, pointing to the possibility of developing TRAIL into a cancer drug[2-4]. This review will summary the molecular mechanisms of TRAIL-induced apoptosis and discuss the questions to be resolved in this field.

Effect of Fuzheng Kang'ai recipe combined with gefitinib on lung cancer A549 cells and its mechanism research

Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Methods The effects of FKR(0.211,0.316,0.474,0.711,1.067,1.600,2.400,3.600 mg/mL)combined with