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Yield strength of human erythrocyte membranes to impulsive stretching.

ABSTRACT: Deformability while remaining viable is an important mechanical property of cells. Red blood cells (RBCs) deform considerably while flowing through small capillaries. The RBC membrane can withstand a finite strain, beyond which it ruptures. The classical yield areal strain of 2-4% for RBCs is generally accepted for a quasi-static strain. It has been noted previously that this threshold strain may be much larger with shorter exposure duration. Here we employ an impulse-like forcing to quantify this yield strain of RBC membranes. In the experiments, RBCs are stretched within tens of microseconds by a strong shear flow generated from a laser-induced cavitation bubble. The deformation of the cells in the strongly confined geometry is captured with a high-speed camera and viability is successively monitored with fluorescence microscopy. We find that the probability of cell survival is strongly dependent on the maximum strain. Above a critical areal strain of ?40%, permanent membrane damage is observed for 50% of the cells. Interestingly, many of the cells do not rupture immediately and exhibit ghosting, but slowly obtain a round shape before they burst. This observation is explained with structural membrane damage leading to subnanometer-sized pores. The cells finally lyse from the colloidal osmotic pressure imbalance.

SUBMITTER: Li F

PROVIDER: S-EPMC3752135 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Yield strength of human erythrocyte membranes to impulsive stretching.

Li Fenfang F Chan Chon U CU Ohl Claus Dieter CD

Biophysical journal 20130801 4

Deformability while remaining viable is an important mechanical property of cells. Red blood cells (RBCs) deform considerably while flowing through small capillaries. The RBC membrane can withstand a finite strain, beyond which it ruptures. The classical yield areal strain of 2-4% for RBCs is generally accepted for a quasi-static strain. It has been noted previously that this threshold strain may be much larger with shorter exposure duration. Here we employ an impulse-like forcing to quantify th ...[more]

PMID: 23972839

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Project description:We present a three-dimensional computational study of whole-cell equilibrium shape and deformation of human red blood cell (RBC) using spectrin-level energetics. Random network models consisting of degree-2, 3, ..., 9 junction complexes and spectrin links are used to populate spherical and biconcave surfaces and intermediate shapes, and coarse-grained molecular dynamics simulations are then performed with spectrin connectivities fixed. A sphere is first filled with cytosol and gradually deflated while preserving its total surface area, until cytosol volume consistent with the real RBC is reached. The equilibrium shape is determined through energy minimization by assuming that the spectrin tetramer links satisfy the worm-like chain free-energy model. Subsequently, direct stretching by optical tweezers of the initial equilibrium shape is simulated to extract the variation of axial and transverse diameters with the stretch force. At persistence length p = 7.5 nm for the spectrin tetramer molecule and corresponding in-plane shear modulus mu(0) approximately 8.3 microN/m, our models show reasonable agreement with recent experimental measurements on the large deformation of RBC with optical tweezers. We find that the choice of the reference state used for the in-plane elastic energy is critical for determining the equilibrium shape. If a position-independent material reference state such as a full sphere is used in defining the in-plane energy, then the bending modulus kappa needs to be at least a decade larger than the widely accepted value of 2 x 10(-19) J to stabilize the biconcave shape against the cup shape. We demonstrate through detailed computations that this paradox can be avoided by invoking the physical hypothesis that the spectrin network undergoes constant remodeling to always relax the in-plane shear elastic energy to zero at any macroscopic shape, at some slow characteristic timescale. We have devised and implemented a liquefied network structure evolution algorithm that relaxes shear stress everywhere in the network and generates cytoskeleton structures that mimic experimental observations.

Project description:The microstructure of trabecular bone is usually perceived as a collection of plate-like and rod-like trabeculae, which can be determined from the emerging high-resolution skeletal imaging modalities such as micro-computed tomography (?CT) or clinical high-resolution peripheral quantitative CT (HR-pQCT) using the individual trabecula segmentation (ITS) technique. It has been shown that the ITS-based plate and rod parameters are highly correlated with elastic modulus and yield strength of human trabecular bone. In the current study, plate-rod (PR) finite element (FE) models were constructed completely based on ITS-identified individual trabecular plates and rods. We hypothesized that PR FE can accurately and efficiently predict elastic modulus and yield strength of human trabecular bone. Human trabecular bone cores from proximal tibia (PT), femoral neck (FN) and greater trochanter (GT) were scanned by ?CT. Specimen-specific ITS-based PR FE models were generated for each ?CT image and corresponding voxel-based FE models were also generated in comparison. Both types of specimen-specific models were subjected to nonlinear FE analysis to predict the apparent elastic modulus and yield strength using the same trabecular bone tissue properties. Then, mechanical tests were performed to experimentally measure the apparent modulus and yield strength. Strong linear correlations for both elastic modulus (r(2) = 0.97) and yield strength (r(2) = 0.96) were found between the PR FE model predictions and experimental measures, suggesting that trabecular plate and rod morphology adequately captures three-dimensional (3D) microarchitecture of human trabecular bone. In addition, the PR FE model predictions in both elastic modulus and yield strength were highly correlated with the voxel-based FE models (r(2) = 0.99, r(2) = 0.98, respectively), resulted from the original 3D images without the PR segmentation. In conclusion, the ITS-based PR models predicted accurately both elastic modulus and yield strength determined experimentally across three distinct anatomic sites. Trabecular plates and rods accurately determine elastic modulus and yield strength of human trabecular bone.

Project description:Background: In animal studies long-term stretching interventions up to several hours per day have shown large increases in muscle mass as well as maximal strength. The aim of this study was to investigate the effects of a long-term stretching on maximal strength, muscle cross sectional area (MCSA) and range of motion (ROM) in humans. Methods: 52 subjects were divided into an Intervention group (IG, n = 27) and a control group (CG, n = 25). IG stretched the plantar flexors for one hour per day for six weeks using an orthosis. Stretching was performed on one leg only to investigate the contralateral force transfer. Maximal isometric strength (MIS) and 1RM were both measured in extended knee joint. Furthermore, we investigated the MCSA of IG in the lateral head of the gastrocnemius (LG) using sonography. Additionally, ROM in the upper ankle was investigated via the functional "knee to wall stretch" test (KtW) and a goniometer device on the orthosis. A two-way ANOVA was performed in data analysis, using the Scheffé Test as post-hoc test. Results: There were high time-effects (p = 0.003, ƞ² = 0.090) and high interaction-effect (p < 0.001, ƞ²=0.387) for MIS and also high time-effects (p < 0.001, ƞ²=0.193) and interaction-effects (p < 0.001, ƞ²=0,362) for 1RM testing. Furthermore, we measured a significant increase of 15.2% in MCSA of LG with high time-effect (p < 0.001, ƞ²=0.545) and high interaction-effect (p=0.015, ƞ²=0.406). In ROM we found in both tests significant increases up to 27.3% with moderate time-effect (p < 0.001, ƞ²=0.129) and high interaction-effect (p < 0.001, ƞ²=0.199). Additionally, we measured significant contralateral force transfers in maximal strength tests of 11.4% (p < 0.001) in 1RM test and 1.4% (p=0.462) in MIS test. Overall, there we no significant effects in control situations for any parameter (CG and non-intervened leg of IG). Discussion: We hypothesize stretching-induced muscle damage comparable to effects of mechanical load of strength training, that led to hypertrophy and thus to an increase in maximal strength. Increases in ROM could be attributed to longitudinal hypertrophy effects, e.g., increase in serial sarcomeres. Measured cross-education effects could be explained by central neural adaptations due to stimulation of the stretched muscles.

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Yield strength of human erythrocyte membranes to impulsive stretching.

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Yield strength of human erythrocyte membranes to impulsive stretching.

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