Biology subjects

Dasanna, A. K.

Publications and source records attributed to Dasanna, A. K..

7 recordsLinked to original sources

bioRxiv2026

Hyaluronan Surface Architecture Dictates Colorectal Cancer Progression and Extracellular Vesicle Communication

Hyaluronan (HA) is a principal component of the tumor glycocalyx in colorectal cancer (CRC). However, how the disease progression is linked to HA abundance and its nanoscale organization remains unclear. Single-molecule measurements of surface glycans on cell membranes and extracellular vesicles (EVs) have not yet been correlated. In this work, using single-molecule force spectroscopy, we mapped HA density and chain length on CRC cells and their EVs across Dukes' stages. HA density increased with stage in both compartments, but their organization diverged. Cell-surface HA became progressively fragmented, whereas EVs remained enriched in short HA chains at every stage. EVs, therefore, appear to select HA during formation rather than inherit it from the parent cell. This divergence had mechanical consequences. Both cells and EVs softened with stage, and removing HA reversed this softening. In addition, coarse-grained membrane simulations revealed that both HA chain length and surface density regulate membrane wrapping, with chain length primarily influencing wrapping kinetics and surface density affecting the final wrapping extent. These findings provide a physical basis for the differences we observed in EV uptake. Reprogramming stage D cells with exogenous high-molecular-weight HA reversed this signature, lowering EV surface HA density, stiffening the vesicles, slowing migration, and suppressing EV uptake by recipient cells. These findings establish HA surface architecture as a stage-encoded and experimentally reversible determinant of CRC progression.

biophysics↗

bioRxiv2025

Modelling Actin-MT Crosstalk in Migrating Cells

Actin-Microtubule crosstalk regulates the polarity and morphology of migrating cells and encompasses mechanical interactions, mediated by crosslinkers, molecular motors, and cytoskeletal regulators. Recent experiments indicate that local microtubule depolymerization promotes local actomyosin retraction, whereas local microtubule polymerization promotes local actin-polymerization. Based on these observations, we develop a computational whole-cell model involving dynamic microtubules interacting mechanically and chemically with an active cell boundary. Specifically, the tips of microtubules send signals for local expansion or contraction to the active cell boundary, depending on whether they are in the growth or shrink phase. A rich, self-organized, dynamic behavior emerges, characterized by the repositioning of the microtubule-organizing center relative to the nucleus and the direction of migration. This also includes a variety of migration patterns, cell morphologies, and complex responses to obstacles in microfluidic and obstacle park environments. We demonstrate that microtubule length and cell boundary stiffness have a significant impact on these features, highlighting the need for new experimental investigations. Thus, the model provides a unified framework that explains a wide range of experimental observations and setups where actin-microtubule crosstalk plays a crucial role.

biophysics↗

bioRxiv2024

Adhesion-driven vesicle translocation through membrane-covered pores

Translocation across barriers and through constrictions is a mechanism that is often used in vivo for transporting material between compartments. A specific example is apicomplexan parasites invading host cells through the tight junction that acts as a pore, and a similar barrier crossing is involved in drug delivery using lipid vesicles on the skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii. The vesicles bind to a lipid bilayer spanning the pore, and the adhesion-energy gain drives the translocation; the vesicle deformation while squeezing through leads to an energy barrier. In addition, the deformation-energy cost for deforming the pore-spanning membrane hinders translocation. Increasing the bending rigidity of the pore-spanning membrane and decreasing the pore size both increase the barrier height and shift the maximum to smaller translocation fractions. We compare the translocation of initially spherical vesicles with fixed membrane area and freely adjustable volume to that of initially prolate vesicles with fixed membrane area and volume. In the latter case, translocation can be entirely suppressed. Our predictions may help rationalize the invasion of apicomplexan parasites into host cells and design measures to combat the diseases they transmit.

biophysics↗

bioRxiv2022

The role of hydrodynamic flow in the self-assembly of dragline spider silk proteins

Hydrodynamic flow in the spider duct induces conformational changes in dragline spider silk proteins (spidroins) and drives their assembly, but the underlying physical mechanisms are still elusive. Here we address this challenging multiscale problem with a complementary strategy of atomistic and coarse-grained Molecular Dynamics (MD) simulations with uniform flow. The conformational changes at the molecular level were analyzed for single tethered spider silk peptides. Uniform flow leads to coiled-to-stretch transitions and pushes alanine residues into {beta}-sheet and Poly-Proline II (PPII) conformations. Coarse-grained simulations of the assembly process of multiple semi-flexible block copolymers using multi-particle collision dynamics reveal that the spidroins aggregate faster but into low-order assemblies when they are less extended. At medium-to-large peptide extensions (50%-80%), assembly slows down and becomes reversible with frequent association and dissociation events, while spidroin alignment increases and alanine repeats form ordered regions. Our work highlights the role of flow in guiding silk self-assembly into tough fibers by enhancing alignment and kinetic reversibility, a mechanism likely relevant for other proteins whose function depends on hydrodynamic flow.

biophysics↗

bioRxiv2021

Effect of malaria parasite shape on its alignment at erythrocyte membrane

During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasites apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically un-favorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasites shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, spherical parasite aligns faster than any other investigated shapes. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes, but is more robust with respect to different adhesion interactions and RBC membrane rigidities.

biophysics↗

bioRxiv2021

Importance of viscosity contrast for the motion of erythrocytes in microcapillaries

The dynamics and deformation of red blood cells (RBCs) in microcirculation affect the flow resistance and transport properties of whole blood. One of the key properties that can alter RBC dynamics in flow is the contrast {lambda} (or ratio) of viscosities between RBC cytosol and blood plasma. Here, we study the dependence of RBC shape and dynamics on the viscosity contrast in tube flow, using mesoscopic hydrodynamics simulations. State diagrams of different RBC dynamical states, including tumbling cells, parachutes, and tank-treading slippers, are constructed for various viscosity contrasts and wide ranges of flow rates and tube diameters (or RBC confinements). Despite similarities in the classification of RBC behavior for different viscosity contrasts, there are notable differences in the corresponding state diagrams. In particular, the region of parachutes is significantly larger for {lambda} = 1 in comparison to {lambda} = 5. Furthermore, the viscosity contrast strongly affects the tumbling-to-slipper transition, thus modifying the regions of occurrence of these states as a function of flow rate and RBC confinement. Also, an increase in cytosol viscosity leads to a reduction in membrane tension induced by flow stresses. Physical mechanisms that determine these differences in RBC dynamical states as a function of {lambda} are discussed.

biophysics↗

bioRxiv2020

Stochastic bond dynamics facilitates alignment of malaria parasite at erythrocyte membrane upon invasion

Malaria parasites invade healthy red blood cells (RBCs) during the blood stage of the disease. Even though parasites initially adhere to RBCs with a random orientation, they need to align their apex toward the membrane in order to start the invasion process. Using hydrodynamic simulations of a RBC and parasite, where both interact through discrete stochastic bonds, we show that parasite alignment is governed by the combination of RBC membrane deformability and dynamics of adhesion bonds. The stochastic nature of bond-based interactions facilitates a diffusive-like re-orientation of the parasite at the RBC membrane, while RBC deformation aids in the establishment of apexmembrane contact through partial parasite wrapping by the membrane. This bond-based model for parasite adhesion quantitatively captures alignment times measured experimentally and demonstrates that alignment times increase drastically with increasing rigidity of the RBC membrane. Our results suggest that the alignment process is mediated simply by passive parasite adhesion.

biophysics↗