The plant actin cytoskeleton is an unstable network of filaments that influences polarized growth through poorly understood mechanisms. Here, we used a combination of live cell imaging and finite element computational modelling of Arabidopsis trichome morphogenesis to determine how the actin and microtubule cytoskeletons cooperate to pattern the cell wall and growth. The actin-related protein (ARP)2/3 complex generates an actin meshwork that operates within a tip-localized, microtubule-depleted zone to modulate cell wall anisotropy locally. The actin meshwork also positions an actin bundle network that organizes organelle flow patterns. This activity is required to maintain cell wall thickness gradients that enable tip-biased diffuse growth. These newly discovered couplings between cytoskeletal patterns and wall textures provide important insights into the cellular mechanism of growth control in plants.
In situ longitudinal (axial) pre-stretch (LPS) plays a fundamental role in the mechanics of the femoropopliteal artery (FPA). It conserves energy during pulsation and prevents buckling of the artery during limb movement. We investigated how LPS is affected by demographics and risk factors, and how these patient characteristics associate with the structural and physiologic features of the FPA. LPS was measured in n=148 fresh human FPAs (14–80 years old). Mechanical properties were characterized with biaxial extension and histopathological characteristics were quantified with Verhoeff-Van Gieson Staining. Constitutive modeling was used to calculate physiological stresses and stretches which were then analyzed in the context of demographics, risk factors and structural characteristics. Age had the strongest negative effect (r=−0.812, p<0.01) on LPS and could alone explain 66% of LPS variability. Male gender, higher body mass index, hypertension, diabetes, coronary artery disease, dyslipidemia and tobacco use had negative effects on LPS, but only the effect of tobacco was not associated with aging. FPAs with less pre-stretch had thicker medial layers, but thinner intramural elastic fibers with less dense and more fragmented external elastic laminae. Elastin degradation was associated with decreased physiological tethering force and longitudinal stress, while circumferential stress remained constant. FPA wall pathology was negatively associated with LPS (r = −0.553, p<0.01), but the effect was due primarily to aging. LPS in the FPA may serve as an energy reserve for adaptive remodeling. Reduction of LPS due to degradation and fragmentation of intramural longitudinal elastin during aging can be accelerated in tobacco users.
Introduction Femoropopliteal artery (FPA) mechanics play a paramount role in pathophysiology and the artery’s response to therapeutic interventions, but data on FPA mechanical properties are scarce. Our goal was to characterize human FPAs over a wide population to derive a constitutive description of FPA ageing to be used for computational modeling. Methods Fresh human FPA specimens (n=579) were obtained from n=351 predominantly male (80%) donors 54±15 years old (range 13–82 years). Morphometric characteristics including radius, wall thickness, opening angle, and longitudinal pre-stretch were recorded. Arteries were subjected to multi-ratio planar biaxial extension to determine constitutive parameters for an invariant-based model accounting for the passive contributions of ground substance, elastin, collagen and smooth muscle. Nonparametric bootstrapping was used to determine unique sets of material parameters that were used to derive age-group-specific characteristics. Physiologic stress-stretch state was calculated to capture changes with ageing. Results Morphometric and constitutive parameters were derived for seven age groups. Vessel radius, wall thickness, and circumferential opening angle increased with ageing, while longitudinal pre-stretch decreased (p<0.01). Age-group-specific constitutive parameters portrayed orthotropic FPA stiffening, especially in the longitudinal direction. Structural changes in artery wall elastin were associated with reduction of physiologic longitudinal and circumferential stretches and stresses with age. Conclusions These data and the constitutive description of FPA ageing shed new light on our understanding of peripheral arterial disease pathophysiology and arterial ageing. Application of this knowledge might improve patient selection for specific treatment modalities in personalized, precision medicine algorithms and could assist in device development for treatment of peripheral artery disease.
High failure rates of Peripheral Arterial Disease (PAD) stenting appear to be associated with the inability of certain stent designs to accommodate severe biomechanical environment of the femoropopliteal artery (FPA) that bends, twists, and axially compresses during limb flexion. Twelve Nitinol stents (Absolute Pro, Supera, Lifestent, Innova, Zilver, Smart Control, Smart Flex, EverFlex, Viabahn, Tigris, Misago, and Complete SE) were quasi-statically tested under bench-top axial and radial compression, axial tension, bending, and torsional deformations. Stents were compared in terms of force-strain behavior, stiffness, and geometrical shape under each deformation mode. Tigris was the least stiff stent under axial compression (6.6, N/m axial stiffness) and bending (0.1 N/m) deformations, while Smart Control was the stiffest (575.3 N/m and 105.4 N/m, respectively). Under radial compression Complete SE was the stiffest (892.8 N/m), while Smart Control had the lowest radial stiffness (211.0 N/m). Viabahn and Supera had the lowest and highest torsional stiffness (2.2 µN·m/° and 959.2 µN·m/°), respectively. None of the 12 PAD stents demonstrated superior characteristics under all deformation modes and many experienced global buckling and diameter pinching. Though it is yet to be determined which of these deformation modes might have greater clinical impact, results of the current analysis may help guide development of new stents with improved mechanical characteristics.
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