Mobility of alpha-actinin along growing actin filaments might affect the cellular chirality

Chirality is a widespread feature existing in nature and can be critical in the proper functions of some organisms. In our previous work, a rotational clutch-filament model for a radial fiber was built to reveal the critical role of α-actinin in the cellular chiral swirling. Here we assume two mobility modes of α-actinin along actin filaments. In Mode A, where α-actinin concomitantly moves together with a growing filament, our model analysis suggests that cells cannot swirl clockwise; in Mode B, where α-actinin is fixed along the axial direction of the radial fiber instead, our model analysis suggests that both counter-clockwise and clockwise chiral swirling occur, in consistency with experiments. Thus, our studies suggest that how α-actinin moves along growing filaments within a radial fiber would strongly affect cellular swirling. In addition, the previous rotational clutch-model has been improved by considering the elastic response of a radial fiber to a torque and distributed biomechanical properties of varied cell phenotype.

Switching Cellular Swirling Upon One-Way Torsional Drive

In understanding how a radially symmetrical actin cytoskeleton spontaneously evolves into a chiral system, here we construct a torsional clutch-filament model for one radial fiber. The model analysis indicates that when actin filaments in growth tend to actively drive the radial fiber to only rotate counter-clockwise, certain amount of passive elastic energy also builds up within the radial fiber upon filament growth, the release of which tends to drive it to rotate clockwise. The competition between these two sources would eventually determine the cellular swirling direction, which can be counter-clockwise or clockwise. The model prediction is in consistency with recent experimental findings. This work provides understanding into how the cellular chirality can be modulated by varied molecular components associated with the cytoskeleton.

429 Right ventricular longitudinal and radial fiber contractility in patients undergoing mitral valve surgery: a PREPARE-MVR substudy

Severe mitral regurgitation results in significant hemodynamic demands of not only the left, but the right ventricle (RV) as well. Increased pulmonary pressures and consequential pressure overload of the RV induces complex remodeling, which can be partially restored by mitral valve repair/replacement (MVR). MVR is associated with marked changes of RV deformation, however, the clinical significance of these changes is not well estabilished. The PREPARE-MVR study (PRediction of Early PostoperAtive Right vEntricular failure in Mitral Valve Replacement/Repair patients) aims to determine parameters, which may predict the perioperative risk of acute RV failure. In this current substudy, our aim was to determine the changes of RV global, longitudinal and radial fiber contractility before and following MVR. Our study group consisted of 27 MVR patients (mean age: 64 ± 12 years, m/f: 19/8). Transthoracic 3D echocardiography was performed before the operation and following intensive care unit discharge. 3D beutel model of the RV was created and RV end-diastolic volume index (EDVi) among with RV ejection fraction (RVEF) were calculated using commercially available software. For in-depth analysis of RV mechanics, we have decomposed the motion of the RV using our custom software (ReVISION) to determine longitudinal (LEF) and radial ejection fraction (REF). Right heart catheterization was also performed before MVR and 24 hours after MVR as well to measure pulmonary arterial mean systolic pressure (mPAP), pulmonary arterial wedge pressure (PAWP) and RV stroke work index (RVSWi). Using the aforementioned parameters, we have calculated RV longitudinal (longRVSWi) and RV radial stroke work index (radRVSWi), which represent RV longitudinal and radial fiber contractility. RV morphology did not change significantly according to RVEDVi (preop vs. postop: 71 ± 17 vs. 72 ± 20 mL/m², p = NS). RVEF slightly decreased after MVR (50 ± 6 vs. 48 ± 7 %, p < 0.05), however, RV motion pattern markedly changed. Postoperative LEF was significantly lower compared to preoperative values (25 ± 6 vs. 16 ± 6%, p < 0.0001), among with an increase in REF (21 ± 7 vs. 27 ± 7%, p < 0.01). As expected, mPAP and PAWP decreased in response to MVR (mPAP: 30 ± 10 vs. 25 ± 7 mmHg; PAWP: 19 ± 7 vs. 13 ± 3 mmHg, both p < 0.01). Global RV contractility decreased after surgery (RVSWi: 603 ± 355 vs. 474 ± 251 mmHg*mL/m², p < 0.05). While RV longitudinal contractility also significantly reduced (longRVSWi: 289 ± 179 vs. 166 ± 122 mmHg*mL/m², p < 0.001), radial contractility was maintained following MVR (radRVSWi: 240 ± 141 vs. 261 ± 144 mmHg*mL/m², p = NS). MVR is associated with marked changes of RV function and hemodynamics. RV longitudinal and radial contractility have distinct response to surgery, which may be important in postoperative patient management. The PREPARE-MVR study aims to examine the role of preoperative RV mechanics in clinical outcome.

The Mechanical Role of the Radial Fiber Network Within the Annulus Fibrosus of the Lumbar Intervertebral Disc: A Finite Elements Study

The annulus fibrosus (AF) of the intervertebral disc (IVD) consists of a set of concentric layers composed of a primary circumferential collagen fibers arranged in an alternating oblique orientation. Moreover, there exists an additional secondary set of radial translamellar collagen fibers which connects the concentric layers, creating an interconnected fiber network. The aim of this study was to investigate the mechanical role of the radial fiber network. Toward that goal, a three-dimensional (3D) finite element model of the L3–L4 spinal segment was generated and calibrated to axial compression and pure moment loading. The AF model explicitly recognizes the two heterogeneous networks of fibers. The presence of radial fibers demonstrated a pronounced effect on the local disc responses under lateral bending, flexion, and extension modes. In these modes, the radial fibers were in a tensile state in the disc region that subjected to compression. In addition, the circumferential fibers, on the opposite side of the IVD, were also under tension. The local stress in the matrix was decreased in up to 9% in the radial fibers presence. This implies an active fiber network acting collectively to reduce the stresses and strains in the AF lamellae. Moreover, a reduction of 26.6% in the matrix sideways expansion was seen in the presence of the radial fibers near the neutral bending axis of the disc. The proposed biomechanical model provided a new insight into the mechanical role of the radial collagen fibers in the AF structure. This model can assist in the design of future IVD substitutes.