3-D Nanomechanics of an Erythrocyte Junctional Complex in Equibiaxial and Anisotropic Deformations

Vera, Carlos; Skelton, R. T.; Bossens, Frédéric; Sung, Lanping Amy

doi:10.1007/s10439-005-4698-y

Cited by 59 publications

(73 citation statements)

References 38 publications

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“…Many proteins with functions to withstand mechanical stresses have modular architectures, i.e., they are composed of tandem-linked domains that are individually folded. The force-induced unfolding/refolding and deformation of these domains regulate the tensions in the protein molecules as required by the cellular processes, such as titin during muscle stretch (Granzier and Labeit 2004), fibronectin in the assembly and cell attachment of the extracellular matrix (Erickson 2002;Oberhauser et al 2002), and spectrin in the deformation of erythrocytes (Vera et al 2005). One common feature in the aforementioned biological processes is that they involve protein molecules in deformed or unfolded conformations.…”

Section: Biological Implications Of the Experimental Resultsmentioning

confidence: 99%

The effects of macromolecular crowding on the mechanical stability of protein molecules

et al. 2008

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Macromolecular crowding, a common phenomenon in the cellular environments, can significantly affect the thermodynamic and kinetic properties of proteins. A single-molecule method based on atomic force microscopy (AFM) was used to investigate the effects of macromolecular crowding on the forces required to unfold individual protein molecules. It was found that the mechanical stability of ubiquitin molecules was enhanced by macromolecular crowding from added dextran molecules. The average unfolding force increased from 210 pN in the absence of dextran to 234 pN in the presence of 300 g/L dextran at a pulling speed of 0.25 mm/sec. A theoretical model, accounting for the effects of macromolecular crowding on the native and transition states of the protein molecule by applying the scaled-particle theory, was used to quantitatively explain the crowding-induced increase in the unfolding force. The experimental results and interpretation presented could have wide implications for the many proteins that experience mechanical stresses and perform mechanical functions in the crowded environment of the cell.

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Section: Biological Implications Of the Experimental Resultsmentioning

confidence: 99%

The effects of macromolecular crowding on the mechanical stability of protein molecules

et al. 2008

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“…Recently, other groups have found that the red blood cell membrane, which has a structure similar to that of the submembranous 'cortical' cytoskeleton of nucleated cells, can be effectively modeled as a tensegrity as well (Vera et al, 2005). On a smaller size scale, the geodesic nuclear lamina and mitotic spindle composed of microtubule struts that push out against a tensed mechanically continuous network of chromosomes and linked nuclear matrix scaffolds (Maniotis et al, 1997a) also have been described as prestressed tensegrity structures Pickett-Heaps et al, 1997).…”

Section: Tensegrity and Cellular Mechanotransductionmentioning

confidence: 99%

Tensegrity-based mechanosensing from macro to micro

Ingber

2008

Progress in Biophysics and Molecular Biology

390

286

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This article is a summary of a lecture on cellular mechanotransduction that was presented at a symposium on "Cardiac Mechano-Electric Feedback and Arrhythmias" that convened at Oxford, England in April 2007. Although critical mechanosensitive molecules and cellular components, such as integrins, stretch-activated ion channels, and cytoskeletal filaments, have been shown to contribute to the response by which cells convert mechanical signals into a biochemical response, little is known about how they function in the structural context of living cells, tissues and organs to produce orchestrated changes in cell behavior in response to stress. Here, studies are reviewed that suggest our bodies use structural hierarchies (systems within systems) composed of interconnected extracellular matrix and cytoskeletal networks that span from the macroscale to the nanoscale to focus stresses on specific mechanotransducer molecules. A key feature of these networks is that they are in a state of isometric tension (i.e., experience a tensile prestress), which ensures that various molecular-scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response. These features of living architecture are the same principles that govern tensegrity (tensional integrity) architecture, and mathematical models based on tensegrity are beginning to provide new and useful descriptions of living materials, including mammalian cells. This article reviews how the use of tensegrity at multiple size scales in our bodies guides mechanical force transfer from the macro to the micro, as well as how it facilitates conversion of mechanical signals into changes in ion flux, molecular binding kinetics, signal transduction, gene transcription, cell fate switching and developmental patterning.

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“…This model could then be used in studying RBCs with cytoskeletal defects which are typical in blood disorders such as hereditary spherocytosis and elliptocytosis (25,26). The present work thus seeks to provide a significant advance over previous models that were either formulated at the continuum scale (18), thereby ignoring the discrete cytoskeletal structure, or that assumed a fixed cytoskeleton connectivity (14,19,(27)(28)(29)(30), thereby useful only to study elastic cell deformation without any dynamic cytoskeletal remodeling due to mechanical, thermal, or chemical driving forces.…”

mentioning

confidence: 91%

“…The novelty of this model over prior spectrin-based simulations (14,19,(27)(28)(29)(30) is that the A-B association is breakable, as well as reformable, with the network topology changing dynamically. Under increasing tensile force, the A-B association breaks when their distance reaches the inflexion point of V AB (r), r inflexion ϭ (26/7) 1/6 , indicated as the red circle in Fig.…”

Section: Computational Modelmentioning

confidence: 99%

Cytoskeletal dynamics of human erythrocyte

Lykotrafitis²,

Dao³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

241

201

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The human erythrocyte (red blood cell, RBC) demonstrates extraordinary ability to undergo reversible large deformation and fluidity. Such mechanical response cannot be consistently rationalized on the basis of fixed connectivity of the cell cytoskeleton that comprises the spectrin molecular network tethered to phospholipid membrane. Active topological remodeling of spectrin network has been postulated, although detailed models of such dynamic reorganization are presently unavailable. Here we present a coarsegrained cytoskeletal dynamics simulation with breakable protein associations to elucidate the roles of shear stress, specific chemical agents, and thermal fluctuations in cytoskeleton remodeling. We demonstrate a clear solid-to-fluid transition depending on the metabolic energy influx. The solid network's plastic deformation also manifests creep and yield regimes depending on the strain rate. This cytoskeletal dynamics model offers a means to resolve long-standing questions regarding the reference state used in RBC elasticity theory for determining the equilibrium shape and deformation response. In addition, the simulations offer mechanistic insights into the onset of plasticity and void percolation in cytoskeleton. These phenomena may have implication for RBC membrane loss and shape change in the context of hereditary hemolytic disorders such as spherocytosis and elliptocytosis.cytoskeleton remodeling ͉ computer simulation ͉ fluidization ͉ plasticity ͉ spectrin-actin dissociation D uring its 120-day life span, a red blood cell (RBC) circulates a million times in human body, often squeezing through narrow capillaries. The erythrocyte's remarkable mechanical properties originate from the unique architecture of its cell wall, which is the main load bearing component as there are no stress fibers inside the cell. The cell wall comprises a spectrin tetramer network tethered to a phospholipid bilayer (1, 2). It is very flexible, and yet resilient enough to recover the biconcave shape whenever the cell is quiescent (see Fig. 1). It has been proposed that the spectrin network connectivity is not fixed and can experience extensive remodeling as the RBC undergoes large deformation. Experiments show that, under physiological conditions, the spectrin tetramers in an unstressed intact cell wall exist in rapid dynamic equilibrium with the dimers, and that shear-induced cell wall deformation displaces the balance in favor of the dimers (3). Here, the cell wall behaves as a weak elastic solid at low strain levels, whereas it can be fluidized beyond a certain level of shear deformation, similar to soft matter such as emulsions and colloidal pastes (4, 5). Upon unloading, the dynamic stability is shifted toward tetramers and the stiffness of the cell wall increases. Experiments also suggest that cytoskeleton remodeling can be regulated by biochemical factors such as Ca 2ϩ and ATP (adenosine 5Ј-triphosphate) concentrations (6, 7). It has been postulated that phosphorylation affects spectrin-actin binding and produces changes i...

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3-D Nanomechanics of an Erythrocyte Junctional Complex in Equibiaxial and Anisotropic Deformations

Cited by 59 publications

References 38 publications

The effects of macromolecular crowding on the mechanical stability of protein molecules

The effects of macromolecular crowding on the mechanical stability of protein molecules

Tensegrity-based mechanosensing from macro to micro

Cytoskeletal dynamics of human erythrocyte

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