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Aljapur, V.

Publications and source records attributed to Aljapur, V..

3 recordsLinked to original sources

Tau-Mediated Cytoskeletal Stabilization Modulates Cell Mechanics and Vulnerability to Mechanical Strain

Cells experience mechanical loading across a broad range of loading rates, from low strain rates that are generated during morphogenesis and tissue remodelling, to high and injurious strain rates that are sustained during ventilation-induced lung injury, blast-induced injury, and impact-induced traumatic brain injury. Cell survival under high strain rate loading conditions depends on the ability of the cytoskeleton and plasma membrane to sustain mechanical load without permanent damage. The activity of different cytoskeletal and membrane regulatory proteins could therefore modulate cell susceptibility to injury, but the underlying mechanisms of injury at high strain rate are poorly understood. Tau is a microtubule-associated protein best known for its role in stabilizing microtubules in neurons and as a marker of neurodegenerative disease. Here, we investigated how Tau expression, phosphorylation, and microtubule binding modulates cell viscoelastic behaviour and membrane integrity during high strain-rate uniaxial stretch. We show that Tau expression and de-phosphorylation stabilize microtubules and causes increases in cell stiffness, suppresses cytoskeletal fluidity, and heightens susceptibility to stretch-induced membrane poration. Interestingly, we also find that these effects cannot be explained by microtubule stabilization by Tau alone. Actin architecture acts as a key determinant of injury vulnerability at high strain rate, highlighting the importance of cytoskeletal fluidity and microtubule-actin crosstalk for rapid force dissipation. Significance StatementCells must rapidly adapt to mechanical stress during high strain rate deformation. This study shows that Tau, a microtubule-associated protein, modulates cellular mechanics by increasing stiffness, decreasing viscoelastic fluidity, and enhancing susceptibility to membrane poration under rapid stretch. While Tau-mediated microtubule stabilization contributes to these effects, actin architecture and microtubule-actin crosstalk are also critical determinants of injury vulnerability in Tau-expressing cells.

biophysics↗

FAST: Filamentous Actin Segmentation Tool for quantifying cytoskeletal organization

Studying how actin filaments are assembled into different subcellular structures can provide insights into both physiological processes and the mechanisms of disease. However, quantifying the size, abundance, and organization of different classes of actin structure from optical microscopy data remains a challenge. To address this, we developed a deep learning based Filamentous Actin Segmentation Tool (FAST) to accurately and efficiently segment and quantify different classes of actin structure from phalloidin stained confocal microscopy images. We evaluated the performance of this tool to segment and quantify the abundance of different classes of actin structure in different cell lines and with dynamic changes in actin organization using lifeact-GFP during drug treatments. FAST enables quantification of different classes of actin structure from actin images alone, without the need for specific antibodies against proteins in different actin structures and hence can be a useful tool for researchers studying for studying actin related pathways involved in cell motility, cancer metastasis, and drug development. Summary StatementWe developed Filamentous Actin Segmentation Tool (FAST), that leverages deep learning and antibody assisted labeling to segment and quantify actin structures from optical microscopy images.

cell biology↗

Automated measurement of long-term bower behaviors in Lake Malawi cichlids using depth sensing and action recognition

Measuring naturalistic behaviors in laboratory settings is difficult, and this hinders progress in understanding decision-making in response to ecologically-relevant stimuli. In the wild, many animals manipulate their environment to create architectural constructions, which represent a type of extended phenotype affecting survival and/or reproduction, and these behaviors are excellent models of goal-directed decision-making. Here, we describe an automated system for measuring bower construction in Lake Malawi cichlid fishes, whereby males construct sand structures to attract mates through the accumulated actions of thousands of individual sand manipulation decisions over the course of many days. The system integrates two orthogonal methods, depth sensing and action recognition, to simultaneously measure the developing bower structure and classify the sand manipulation decisions through which it is constructed. We show that action recognition accurately (>85%) classifies ten sand manipulation behaviors across three different species and distinguishes between scooping and spitting events that occur during bower construction versus feeding. Registration of depth and video data streams enables topographical mapping of these behaviors onto a dynamic 3D sand surface. The hardware required for this setup is inexpensive (<$250 per setup), allowing for the simultaneous recording from many independent aquariums. We further show that bower construction behaviors are non-uniform in time, non-uniform in space, and spatially repeatable across trials. We also quantify a unique behavioral phenotype in interspecies hybrids, wherein males sequentially express both phenotypes of behaviorally-divergent parental species. Our work demonstrates that simultaneously tracking both structure and behavior provides an integrated picture of long-term goal-directed decision-making in a naturalistic, dynamic, and social environment.

animal behavior and cognition↗