Stiffening Response Research Articles

Survivin is a Mechanosensitive Regulator of Vascular Smooth Muscle Cell Proliferation

Arterial stiffness induces pathological vascular smooth muscle cell (VSMC) phenotypes, causing atherogenesis and arterial stenosis when rigid arterial extracellular matrix signals VSMCs to aberrantly proliferate. Survivin is an inhibitor of apoptosis but alternatively promotes cell proliferation, and mounting evidence points to survivin inhabiting a key role in vascular injury and stiffening responses. Thus, we seek to understand if survivin plays a role in how mechanical forces drive the pathological proliferation of VSMCs.

Reinforced fibrous recycled aggregate concrete element subjected to uniaxial tensile loading

In this study, effect of recycled aggregates and polypropylene fibers on the response of conventionally reinforced concrete element subjected to tensile loading in terms of tension stiffening and strain development was experimentally investigated. For this purpose, concrete prisms of 100x100 mm cross section and 500 mm length having one central deformed steel re-bar were cast using fibrous and non-fibrous Recycled Aggregate Concrete (RAC) with varying percentages of recycled aggregates (0%, 25%, 50%, 75% and 100%) and tested under uniaxial tensile load. For all fibrous RAC mixes, polypropylene fibers were used at constant dosage of 3.15 kg/m3. Effect of recycled aggregates and fibers on the compressive strength of concrete was also explored in this study. Through studying tensile load versus global axial deformation of composite and strain development in concrete and steel, it was found that replacement of natural aggregates with recycled aggregates in concrete negatively affected the cracking load, tension stiffening and strain development, and this negative effect was observed to be increased with increasing contents of recycled aggregates in concrete. The results of this study showed that it was possible to minimize the negative effect of recycled aggregates in concrete by the addition of polypropylene fibers. Reinforced concrete element constructed using concrete containing 50% recycled aggregates and polypropylene fibers exhibited cracking behavior, tension stiffening and strain development response almost similar to that of concrete element constructed using natural aggregate concrete without fiber.

Strain softening and stiffening responses of spider silk fibers probed using a Micro-Extension Rheometer

Spider silk possesses unique mechanical properties like large extensibility, high tensile strength, super-contractility, etc. Understanding these mechanical responses requires characterization of the rheological properties of silk beyond the simple force-extension relations which are widely reported. Here we study the linear and non-linear viscoelastic properties of dragline silk obtained from social spider Stegodyphus sarasinorum using a Micro-Extension Rheometer that we have developed. Unlike continuous extension data, our technique allows for the probing of the viscoelastic response by applying small perturbations about sequentially increasing steady-state strain values. In addition, we extend our analysis to obtain the characteristic stress relaxation times and the frequency responses of the viscous and elastic moduli. Using these methods, we show that in a small strain regime (0-4%) dragline silk of social spiders shows a strain softening response followed by a strain stiffening response at higher strains (>4%). The stress relaxation time, on the other hand, increases monotonically with increasing strain for the entire range. We also show that the silk stiffens while ageing within the typical lifetime of a web. Our results demand the inclusion of the kinetics of domain unfolding and refolding in the existing models to account for the relaxation time behavior.

Vinculin and metavinculin exhibit distinct effects on focal adhesion properties, cell migration, and mechanotransduction.

Vinculin (Vcn) is a ubiquitously expressed cytoskeletal protein that links transmembrane receptors to actin filaments, and plays a key role in regulating cell adhesion, motility, and force transmission. Metavinculin (MVcn) is a Vcn splice isoform that contains an additional exon encoding a 68-residue insert within the actin binding tail domain. MVcn is selectively expressed at sub-stoichiometic amounts relative to Vcn in smooth and cardiac muscle cells. Mutations in the MVcn insert are linked to various cardiomyopathies. In vitro analysis has previously shown that while both proteins can engage filamentous (F)-actin, only Vcn can promote F-actin bundling. Moreover, we and others have shown that MVcn can negatively regulate Vcn-mediated F-actin bundling in vitro. To investigate functional differences between MVcn and Vcn, we stably expressed either Vcn or MVcn in Vcn-null mouse embryonic fibroblasts. While both MVcn and Vcn were observed at FAs, MVcn-expressing cells had larger but fewer focal adhesions per cell compared to Vcn-expressing cells. MVcn-expressing cells migrated faster and exhibited greater persistence compared to Vcn-expressing cells, even though Vcn-containing FAs assembled and disassembled faster. Magnetic tweezer measurements on Vcn-expressing cells show a typical cell stiffening phenotype in response to externally applied force; however, this was absent in Vcn-null and MVcn-expressing cells. Our findings that MVcn expression leads to larger but fewer FAs per cell, in conjunction with the inability of MVcn to bundle F-actin in vitro and rescue the cell stiffening response, are consistent with our previous findings of actin bundling deficient Vcn variants, suggesting that deficient actin-bundling may account for some of the differences between Vcn and MVcn.

Local Response of Actin Networks is Controlled by Tensile Strains in the Stress-Fibers: Insights From a Discrete Network Model

Using a discrete random network model of the actin cytoskeleton, we studied the effect of stretching of a stiff-fiber on the elastic response of a fibrous network. In real networks, this component can either be a stress-fiber, bundle of fibers within the network, or a microtubule. We analyze the response of this network due to shear loads while the stiff component is under or free of tensile strains. It is observed that the initial response of this network under shear loading is highly dependent on the amount of tensile strain in the stiff-fiber. In addition, the response depends on the amount and the direction of the shear loading, which is either a softening or a stiffening response depending on the loading direction. As a result, the apparent shear modulus of the network containing a preloaded stiff-fiber may become larger or smaller compared to a network with a relaxed stiff-fiber. This effect intensifies for higher levels of tensile strains in the stiff-fiber and for stiffer cross-links, and lessens for higher network densities. The results of the current research are useful in deciphering the response of soft fibrous materials such as the cell cytoskeleton or other networks comprising a random fibrous network containing a stiffer component than the main fibers of the network.

Capturing strain stiffening using Volume Controlled Cavity Expansion

Strain-stiffening is a well-documented behavior in soft biological materials such as liver and brain tissue. Measuring and characterizing this nonlinear response, which is commonly considered as a mechanism for damage prevention, is of great interest to engineers for design of better biomimetic materials, and to physicians for diagnostic purposes. However, probing the elastic response of soft or biological materials at large deformation in their natural habitat, is an arduous task. Here, we present the Volume Controlled Cavity Expansion (VCCE) technique as a measurement method that offers the ability of characterizing the local stiffening response of materials in addition to identifying their shear modulus. By employing minimal constitutive representations involving only two constants (Mooney–Rivlin, Gent, and Ogden) we show that for the conventional PDMS samples, this technique and an accompanying data analysis method capture the shear modulus, as well as providing reliable measures of the stiffening behavior of the samples.

Local exercise does not prevent the aortic stiffening response to acute prolonged sitting: a randomized crossover trial.

Prolonged sitting has been shown to promote endothelial dysfunction in the lower legs. Furthermore, it has been reported that simple sitting-interruption strategies, including calf raises, prevent leg endothelial dysfunction. However, it is unclear whether prolonged sitting affects central cardiovascular health, or whether simple sitting-interruption strategies prevent impaired central cardiovascular health. This study sought to answer two questions: in young, healthy adults 1) does prolonged sitting (3 h) lead to increased aortic stiffness, and 2) do intermittent calf raise exercises to prevent pooling prevent aortic stiffening. Twenty young, healthy participants (21.7 ± 2.5 yr, 70% female, 25.5 ± 6.1 kg/m2) were randomized to 3 h of sitting with (CALF) or without (CON) 10 calf raises every 10 min. Aortic stiffening [carotid-femoral pulse wave velocity (PWV)] was measured in the supine position pre- and post-sitting. Venous pooling during sitting was estimated with total hemoglobin (tHB) concentration using near-infrared spectroscopy. There were no condition × time interactions. Following 3 h of sitting, PWV significantly increased (0.30 ± 0.46 m/s, P < 0.001). There was no condition effect for PWV (P = 0.694), indicating the intermittent calf rises did not preserve central cardiovascular health. tHb was not significantly affected by sitting (P = 0.446) but was 1.9 μM higher for CON versus CALF (P = 0.106). Sitting increases aortic stiffness in young, healthy individuals, a process that may be influenced by lower extremity blood pooling. Calf raises, which have been reported to preserve vascular function in the legs, do not appear to provide sufficient stimulus for maintaining central cardiovascular health.NEW & NOTEWORTHY Although simple strategies, such as fidgeting or calf raises, are sufficient for preserving vascular function in the legs, data from the current study indicate that such strategies are not sufficient for maintaining central cardiovascular health, which is linked to cardiovascular disease.

The superficial zone in cartilage adapts with stiffening when challenged tribologically

Purpose: In osteoarthritis, the superficial zone of articular cartilage is compromised by fissures and cracks and, thus, may lose its intended function. While there is agreement that the superficial zone is important for the load bearing capacity of the tissue, its mechanical response upon articulation is less investigated. In previous studies, using fully intact cartilage samples, we have shown that the cartilage surface undergoes a transient stiffening response upon articulation. Here, we hypothesize that this response is lost when the surface is removed. In order to address this question we used a tribological bioreactor and articulated on cartilage samples with and without superficial zone. Further, we started to study structural changes at the surface with an atomic force microscope (AFM) before and after the application of tribological stress. Methods: Twenty-four 14x20x3 mm oval bovine cartilage explants that had undergone one freeze-thaw cycle were distributed into four groups per animal: (1) intact surface and articular loading; (2) removed surface and articular loading; (3) intact free-swelling-control (FSC); 4) removed surface FSC. Thus, each group had n=6 samples. A vibratome was used to remove the superficial zone of the explants (at least 20% of full sample thickness). Microindentation stress-relaxation tests were performed in the center of explants using a Hysitron TI 950 with a 20 μm spherical indenter and an 8 μm indent depth. All indentation on explants was performed submerged in 1× PBS to maintain tissue hydration. Following initial characterization, cartilage explants were removed from the indentation sample holder and placed into the bioreactor. Cartilage explants were confined in porous polyethylene scaffold rings and fixed in a well. Using a 32-mm ceramic ball (Ra ∼10 nm), a 40 N static confined compression was applied that lead to approx. 2 MPa contact stress. The ball oscillated at 0.5 Hz, and was migrated at a speed of 1mm/s across the cartilage surface generating a wear scar length of 10 mm. Following 1-hr of bioreactor testing, microindentation was repeated in the center/wear scar. The reduced modulus was obtained using the Oliver-Pharr method on 80-95% of the unloading curve. Cartilage surfaces removed by vibratome were prepared for AFM analysis (Nanowizard Ultra, JPK Instruments, Germany). All measurements were conducted in 1× PBS. Using QI imaging, a force sampling mode, an initial image of 256 x 256 pixels (approx. 10 x 10 μm2) was obtained. The AFM was then put into contact mode, and an 80 nm silicon tip was repeatedly (>850 times) slid linearly across the cartilage surface. Following these sliding experiments, the tissue was reimaged in QI mode. For data analysis, the ratio of post- to pre-bioreactor reduced modulus was calculated and analyzed using Shapiro-Wilks tests for normality and Paired Student’s T-tests. Results: Our results show that intact surface groups exhibited significantly increased stiffening following articular loading compared to the FSC (p=0.006). For the removed surface groups, no significant difference between articulated and FSC explants was detected (p=0.927) (Fig 1). Also in the AFM the cartilage surface demonstrated topographical and stiffness related changes upon sliding that are shown in Figure 2. Conclusions: Surface stiffening following tribological loading may be an important biomechanical function of load transfer during articulation. Surface removal leads to a loss of this adaptive response. The stiffening response may be related to a reorganization of matrix molecules that are unique to the superficial zone. In the future we plan to investigate the influencing parameters of this stiffening response and identify the matrix molecules that are involved.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Biomechanical Impact of Localized Corneal Cross-linking Beyond the Irradiated Treatment Area.

To investigate the stiffening effect of localized corneal cross-linking (L-CXL) within and beyond the irradiated region in three dimensions. Ten porcine eyes were debrided of epithelium and incrementally soaked with 0.1% riboflavin solution. Using a customized, sharp-edged mask, half of the cornea was blocked while the other half was exposed to blue light (447 nm). The three-dimensional biomechanical properties of each cornea were then measured via Brillouin microscopy. An imaging system was used to quantify the optimal transition zone between cross-linked and non-cross-linked sections of the cornea when considering light propagation and scattering. A broad transition zone of 610 µm in width was observed between the fully cross-linked and non-cross-linked sections, indicating the stiffening response extended beyond the irradiated region. Light propagation and the scattering induced by the riboflavin-soaked cornea accounted for a maximum of 25 and 159 ± 3.2 µm, respectively. The stiffening effect of L-CXL extends beyond that of the irradiated area. When considering L-CXL protocols clinically, it will be important to account for increased stiffening in surrounding regions. [J Refract Surg. 2019;35(4):253-260.].

Unraveling the high strain-rate dynamic stiffening in select model polyurethanes − the role of intermolecular hydrogen bonding

This study elucidates the influence of molecular attributes on the observed dynamic stiffening in select two-component polyurethanes upon high strain-rate impact. Unlike typical segmented elastomers, polyurethanes consisting of poly(tetramethylene oxide), PTMO, and a diisocyanate, but without a chain extender, are investigated. The hexamethylenediisocyanate (HDI)-based polyurethane, HDI−PU, exhibits crystallinity and a much higher ambient storage modulus, as determined by dynamic mechanical analysis at 1 Hz, than that of 4,4′-methylenediphenyldiisocyanate (MDI)-based polyurethane, MDI−PU. In contrast, MDI−PU exhibits a higher glass transition temperature than that of HDI−PU, and a greater dynamic stiffening against silica micro-particle impacts at strain rates between 107 and 108 s−1. The variation in dynamic stiffening corroborates well the observed dynamics at the molecular level, as determined via solid-state nuclear magnetic resonance (ssNMR) spectroscopy. The presence of a slower-dynamics component in MDI−PU, as evidenced in the 13C ssNMR dipolar dephasing time, is used to explain the observed enhanced dynamic stiffening response.

Mimicking Active Biopolymer Networks with a Synthetic Hydrogel.

Stiffening due to internal stress generation is of paramount importance in living systems and is the foundation for many biomechanical processes. For example, cells stiffen their surrounding matrix by pulling on collagen and fibrin fibers. At the subcellular level, molecular motors prompt fluidization and actively stiffen the cytoskeleton by sliding polar actin filaments in opposite directions. Here, we demonstrate that chemical cross-linking of a fibrous matrix of synthetic semiflexible polymers with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) produces internal stress by induction of a coil-to-globule transition upon crossing the lower critical solution temperature of PNIPAM, resulting in a macroscopic stiffening response that spans more than 3 orders of magnitude in modulus. The forces generated through collapsing PNIPAM are sufficient to drive a fluid material into a stiff gel within a few seconds. Moreover, rigidified networks dramatically stiffen in response to applied shear stress featuring power law rheology with exponents that match those of reconstituted collagen and actomyosin networks prestressed by molecular motors. This concept holds potential for the rational design of synthetic materials that are fluid at room temperature and rapidly rigidify at body temperature to form hydrogels mechanically and structurally akin to cells and tissues.

Synthetic Extracellular Matrices with Nonlinear Elasticity Regulate Cellular Organization.

One of the promises of synthetic materials in cell culturing is that control over their molecular structures may ultimately be used to control their biological processes. Synthetic polymer hydrogels from polyisocyanides (PIC) are a new class of minimal synthetic biomaterials for three-dimensional cell culturing. The macromolecular lengths and densities of biofunctional groups that decorate the polymer can be readily manipulated while preserving the intrinsic nonlinear mechanics, a feature commonly displayed by fibrous biological networks. In this work, we propose the use of PIC gels as cell culture platforms with decoupled mechanical inputs and biological cues. For this purpose, different types of cells were encapsulated in PIC gels of tailored compositions that systematically vary in adhesive peptide (GRGDS) density, polymer length, and concentration; with the last two parameters controlling the gel mechanics. Both cancer and smooth muscle cells grew into multicellular spheroids with proliferation rates that depend on the adhesive GRGDS density, regardless of the polymer length, suggesting that for these cells, the biological input prevails over the mechanical cues. In contrast, human adipose-derived stem cells do not form spheroids but rather spread out. We find that the morphological changes strongly depend on the adhesive ligand density and the network mechanics; gels with the highest GRGDS densities and the strongest stiffening response to stress show the strongest spreading. Our results highlight the role of the nonlinear mechanics of the extracellular matrix and its synthetic mimics in the regulation of cell functions.

Shear Stiffness and Energy Absorption of Auxetic Open Cell Foams as Sandwich Cores

This work describes the identification of the shear modulus of open cell polyurethane thermoformed auxetic foams from 3‐ and 4‐point bending tests. The foams are incorporated in sandwich beams with carbon fibre/epoxy face skins, and benchmarked against similar sandwich structures made with the conventional counterpart open cell foam. Three types of beams are tested: one with auxetic foams, another type related to a conventional foam core with the same thickness of the auxetic porous materials, and a third type of beam consisting in conventional foam with a thickness corresponding to an iso‐weight configuration to the auxetic specimen. The auxetic foam has a shear modulus 7% lower than the one of the bulk conventional specimens, but higher shear stresses at large deformations and a smoother strain stiffening response compared to the beams with the conventional thinner core. The paper also highlights the low shear wave speed of these auxetic foams compared to other porous polymers used in helmet and head protection applications, as well as potential uses of the quasi‐zero‐stiffness behavior here observed for the auxetic foam sandwich beam.

Insight into the tension stiffening behavior of reinforced concrete tension members revealed by finite element modeling

The disasters happened in recent past pointed out the need of design criteria, ensuring adequate safety levels against progressive collapse. The attention was focused on the behavior of composite beam-to-column joint components in the field of large displacements. This article presents the experimental and numerical study enabling the simulation of the RC elements under tension. This has helped in understanding the non-negligible contribution of concrete in tension stiffening response up to failure especially in the case of discontinuous geometry marked in composite structures. The finite element model proposed may be considered a mid-way between smeared and discrete crack modeling approaches.

Role of adsorbed chain rigidity in reinforcement of polymer nanocomposites

ABSTRACTThe thermomechanical behavior of polymer nanocomposites is mostly governed by interfacial properties which rely on particle–polymer interactions, particle loading, and dispersion state. We recently showed that poly(methyl methacrylate) (PMMA) adsorbed nanoparticles in poly(ethylene oxide) (PEO) matrices displayed an unusual thermal stiffening response. The molecular origin of this unique stiffening behavior resulted from the enhanced PEO mobility within glassy PMMA chains adsorbed on nanoparticles. In addition, dynamic asymmetry and chemical heterogeneities existing in the interfacial layers around particles were shown to improve the reinforcement of composites as a result of good interchain mixing. Here, the role of chain rigidity in this interfacially controlled reinforcement in PEO composites is investigated. We show that particles adsorbed with less rigid polymers improve the mechanical properties of composites. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.2019,57, 9–14

Abstract 111: Endothelial Sodium Channel Activation Promotes Angiotensin II Induced Arterial Stiffness and Endothelial Dysfunction

Arterial stiffness is an independent risk factor for the development and progression of cardiovascular and kidney disease. Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) is seen in obesity and contributes significantly to development of arterial stiffness, vascular dysfunction and hypertension. We have recently observed that aldosterone increases the presence of epithelial sodium channels on endothelial cells (EnNaC), which results in stiffening of the endothelial cortical surface (glycocalyx) of the aorta. Accordingly, we posited that deletion of the critical alpha catalytic subunit of EnNaC would decrease Ang II induced arterial stiffening and vascular relaxation responses, in part, via decreases in oxidative stress. To investigate, we used mice with EC cell specific deletion of EnNaC, by serially crossing floxed” EnNaC mice with Tie 2-Cre transgene mice. EnNaC expression was markedly decreased in ECs from EnNaC KO mice while macrophage expression of EnNaC was unaffected. Ang II (500 ng/kg/min) was administered by infusion to 9 month old wild (WT) and EnNaC KO mice for three weeks with or without administration of the antioxidant tempol (2mM/day) in drinking water. Whole cell Na+ currents in ECs, as evaluated by patch clamp, were significantly increased by Ang II infusion, and this was markedly attenuated in EnNAC KO and tempol treated mice. Further, aortic endothelial stiffness as determined by atomic force microscopy was significantly increased in Ang II infused mice and this increase was attenuated in EnNaC KO mice. EnNaC deletion also attenuated impaired acetylcholine (eNOS)-mediated vasorelaxation. Thus, treatment with the antioxidant tempol reduced Ang II induced vascular stiffness and prevented impairment of NO mediated vascular relaxation. Moreover, tempol administration to Ang II infused EnNaC KO mice had similar effects in both Ang II-tempol and Ang II-EnNaC KO groups. Arterial stiffness was significantly decreased by EnNaC deletion or treatment with the antioxidant tempol in femoral vessels as well. These results are consistent with an important role for oxidative stress in Ang II promotion of EnNaC activation, endothelial stiffness and impaired eNOS mediated vascular relaxation.

TGF-β induces changes in breast cancer cell deformability

Mechanical properties of cells are shown to regulate cell behaviors leading to phenotypic changes that may aid in the development and progression of disease. In this study, we used atomic force microscopy (AFM) indentation with a spherical probe to characterize the elastic and viscoelastic properties of invasive (MDA-MB-231) and noninvasive (MCF-7) breast cancer cells treated with transforming growth factor-β (TGF-β). We also used confocal fluorescence imaging to investigate the sub-membrane cytoskeletal structure of the cells. Results showed significant alterations in moduli of both cell types after 24 h TGF-β treatment which had a context dependent response; moduli for MDA-MB-231 decreased whereas MCF-7 demonstrated stiffening response. Stress relaxation tests showed increased fluid-like nature of MDA-MB-231 following TGF-β treatment and lower fluidity for MCF-7 cells. We also observed significant alterations in the expression and orientation of actin stress fibers with TGF-β treatment which correlated with the changes in cell mechanics. Less invasive MCF-7 cells had a delayed overall increase in cell deformability after 48 h exposure to TGF-β; a similar trend was observed for MDA-MB cells. These changes may be important to facilitate migration, for instance, during metastasis of cancer cells through submicron sized spaces.

Thermosensitive biomimetic polyisocyanopeptide hydrogels may facilitate wound repair

Changing wound dressings inflicts pain and may disrupt wound repair. Novel synthetic thermosensitive hydrogels based on polyisocyanopeptide (PIC) offer a solution. These gels are liquid below 16 °C and form gels beyond room temperature. The architecture and mechanical properties of PIC gels closely resemble collagen and fibrin, and include the characteristic stiffening response at high strains. Considering the reversible thermo-responsive behavior, we postulate that PIC gels are easy to apply and remove, and facilitate healing without eliciting foreign body responses or excessive inflammation. Biocompatibility may be higher in RGD-peptide-functionalized PIC gels due to enhanced cell binding capabilities. Full-thickness dorsal skin wounds in mice were compared to wounds treated with PIC gel and PIC-RGD gel for 3 and 7 days. No foreign body reactions and similar wound closure rates were found in all groups. The level of macrophages, myofibroblasts, epithelial migration, collagen expression, and blood vessels did not significantly differ from controls. Surprisingly, granulocyte populations in the wound decreased significantly in the PIC gel-treated groups, likely because foreign bacteria could not penetrate the gel. RGD-peptides did not further improve any effect observed for PIC. The absence of adverse effects, ease of application, and the possibilities for bio-functionalization make the biomimetic PIC hydrogels suitable for development into wound dressings.

Vinculin in Neutrophil Adhesion, Motility and Trafficking

Neutrophils are innate immune effector cells that migrate from the blood to resolve bacterial and fungal infections. Understanding how neutrophils migrate is critical for regulating excessive inflammation and subsequent collateral injury. β2 integrins are essential to classical neutrophil recruitment from the blood, and the activation of β2 integrins has been well defined in previous studies. Adhesion stabilization of neutrophils on the endothelial surface as they crawl into a favorable position for transmigration is not as well defined. Neutrophils do not make mature focal adhesions, but do express the focal adhesion protein vinculin. Vinculin associates with integrins by binding to talin‐1 and stabilizes integrin adhesions by recruiting various actin‐associated proteins or by associating with actin directly. This study characterizes the role of vinculin in neutrophil β2 integrin‐dependent adhesion, motility and anti‐bacterial function. Intrinsic activation of β2 integrins is unaffected by vinculin knockout after CXCL1 activation. Vinculin knockout attenuates neutrophil adhesion, spreading, and motility on glass coated with β2 integrin ligand, ICAM‐1, and activating CXCL1. Vinculin knockout also reduces neutrophil spreading in response to ICAM‐1/CXCL1 on polyacrylamide gels of high stiffness but not lower stiffness. Vinculin knockout reduces traction stresses of neutrophils and the actin stiffening response after stimulation. Unlike static conditions, vinculin knockout does not affect neutrophil motility under flow conditions. Vinculin knockout attenuates respiratory burst, but does not affect phagocytosis. In mixed chimeric mice given intraperitoneal thioglycollate, we find comparable migration of vinculin‐knockout and vinculin‐sufficient neutrophils into the peritoneum. Altogether, while vinculin enhances neutrophil β2 integrin adhesion strength, vinculin knockout does not affect neutrophil motility and trafficking under physiological conditions.Support or Funding InformationAmerican Heart Association (12SDG12080281), Scientist Development Grant CLDepartment of Surgery, Rhode Island HospitalThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Transient response of nonlinear polymer networks: A kinetic theory

Dynamic networks are found in a majority of natural materials, but also in engineering materials, such as entangled polymers and physically cross-linked gels. Owing to their transient bond dynamics, these networks display a rich class of behaviors, from elasticity, rheology, self-healing, or growth. Although classical theories in rheology and mechanics have enabled us to characterize these materials, there is still a gap in our understanding on how individuals (i.e., the mechanics of each building blocks and its connection with others) affect the emerging response of the network. In this work, we introduce an alternative way to think about these networks from a statistical point of view. More specifically, a network is seen as a collection of individual polymer chains connected by weak bonds that can associate and dissociate over time. From the knowledge of these individual chains (elasticity, transient attachment, and detachment events), we construct a statistical description of the population and derive an evolution equation of their distribution based on applied deformation and their local interactions. We specifically concentrate on nonlinear elastic response that follows from the strain stiffening response of individual chains of finite size. Upon appropriate averaging operations and using a mean field approximation, we show that the distribution can be replaced by a so-called chain distribution tensor that is used to determine important macroscopic measures such as stress, energy storage and dissipation in the network. Prediction of the kinetic theory are then explored against known experimental measurement of polymer responses under uniaxial loading. It is found that even under the simplest assumptions of force-independent chain kinetics, the model is able to reproduce complex time-dependent behaviors of rubber and self-healing supramolecular polymers.