Publication InformationRonan, William, Deshpande, Vikram S., McMeeking, Robert M., & McGarry, J. Patrick. (2014). Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion. Biomechanics found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the interdependent biomechanical processes regulating stress fibre and focal adhesion formation.
The biomechanisms that govern the response of chondrocytes to mechanical stimuli are poorly understood. In this study, a series of in vitro tests are performed, in which single chondrocytes are subjected to shear deformation by a horizontally moving probe. Dramatically different probe force -indentation curves are obtained for untreated cells and for cells in which the actin cytoskeleton has been disrupted. Untreated cells exhibit a rapid increase in force upon probe contact followed by yielding behaviour. Cells in which the contractile actin cytoskeleton was removed exhibit a linear force -indentation response. In order to investigate the mechanisms underlying this behaviour, a three-dimensional active modelling framework incorporating stress fibre (SF) remodelling and contractility is used to simulate the in vitro tests. Simulations reveal that the characteristic force -indentation curve observed for untreated chondrocytes occurs as a result of two factors: (i) yielding of SFs due to stretching of the cytoplasm near the probe and (ii) dissociation of SFs due to reduced cytoplasm tension at the front of the cell. In contrast, a passive hyperelastic model predicts a linear force -indentation curve similar to that observed for cells in which the actin cytoskeleton has been disrupted. This combined modelling -experimental study offers a novel insight into the role of the active contractility and remodelling of the actin cytoskeleton in the response of chondrocytes to mechanical loading.
Publication InformationShirazi, RN,Ronan, W,Rochev, Y,McHugh, P (2016) 'Modelling the degradation and elastic properties of poly (lacticco-glycolic
AbstractScaffolding plays a critical rule in tissue engineering and an appropriate degradation rate and sufficient mechanical integrity are required during degradation and healing of tissue. This paper presents a computational investigation of the molecular weight degradation and the mechanical performance of poly(lactic-co-glycolic acid) (PLGA) films and tissue engineering scaffolds. A reactiondiffusion model which predicts the degradation behaviour is coupled with an entropy-based mechanical model which relates the Young's modulus and the molecular weight. The model parameters are determined based on experimental data for in-vitro degradation of a PLGA film. Microstructural models of three different scaffold architectures are used to investigate the degradation and mechanical behaviour of each scaffold. Although the architecture of the scaffold does not have a significant influence on the degradation rate, it determines the initial stiffness of the scaffold. It is revealed that the size of the scaffold strut controls the degradation rate and the mechanical collapse. A critical length scale due to competition between diffusion of degradation products and autocatalytic degradation is determined to be in the range 2-100 μm. Below this range, slower homogenous degradation occurs; however, for larger samples monomers are trapped inside the sample and faster autocatalytic degradation occurs.
Publication InformationReynolds, NH,Ronan, W,Dowling, EP,Owens, P,McMeeking, RM,McGarry, JP (2014) 'On the role of the actin cytoskeleton and nucleus in the biomechanical response of spread cells '. Biomaterials,.
Metallic and polymeric foams typically possess a low tensile failure strain of a few percent despite the fact that the parent solid can have high ductility (10% or more). This is remarkable as foams are bending-dominated in their structural response, and it is widely accepted that beams have a high ductility in bending compared to a bar in uniaxial tension. Possible reasons for this paradox are explored for a 2D hexagonal honeycomb, and for a so-called 'lotus cellular material', made from an elastic-plastic parent solid. Finite element simulations reveal that there is only a small drop in tensile ductility due to the presence of Plateau borders or due to the random misalignment of nodes; a much greater drop in ductility results from missing cell walls (equivalent to misshapen cells) or to the presence of stiff inclusions. The drop in ductility due to inclusions is associated with the multiaxial stress state that exists in their vicinity. This study emphasises the need for a uniform microstructure in order for foams to possess a high macroscopic ductility.
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