Biology subjects

Le, T. B.

Publications and source records attributed to Le, T. B..

4 recordsLinked to original sources

bioRxiv2026

Impacts of Morphology and Elasticity on Cancer Cell Deformation in Shear-flows

PurposeThis work investigates the role of the cancer cell morphology and elasticity on the deformation patterns under shear-flow in a micro-channel. MethodsA novel hybrid continuum-particle framework is developed to simulate cancer-cell dynamics. Cell membrane and nucleus geometries are reconstructed from microscopic images and modeled using Dissipative Particle Dynamics, while the surrounding blood plasma is treated as an incompressible Newtonian fluid. Cell-flow interactions are captured via an immersed boundary method. ResultsAll cancer-cell models exhibited a rapid deformation response within the first 1-2 ms, followed by morphology- and stiffness-dependent shape evolution. The compact morphologies showed strong recovery, whereas the other models evolved toward folded/lobed states with only intermittent partial recovery during shape transitions. Membrane stiffening dominated elongation and compactness loss, while nuclear stiffening modulated deformation excursions and partial recovery. These shape transitions were accompanied by near-field vortex reorganization and traction localization. Similar to deformation response the net membrane force exhibited a common start-up rise within 0-0.5 ms followed by relaxation. Compact morphologies produce lower and steadier forces. They show minimal stiffness dependence. Deformation-prone morphologies show stronger unsteadiness and clearer stiffness modulation. Cross-sectional velocity and vorticity fields showed a dominant x-directed hydrodynamic imbalance and lateral migration. ConclusionOur results demonstrate that morphology sets the stiffness modulated deformation patterns which effects the extracellular flow dynamics and traction. In turn, the resulting flow field and traction distribution feed back to influence subsequent deformation and migration. This mechanistic link provides a framework for interpreting circulating tumor cell transport in shear-dominated metastatic environments.

bioengineering↗

bioRxiv2025

The impacts of shape in lateral migration of cancer cells in a microchannel

This work presents the development of a novel approach to model the dynamics of cancer cells in microcirculation. We investigate the role the membrane elasticity, and cancer cell shape on deformation dynamics under the shear and pressure forces in a micro-channel. The proposed numerical model is based on a hybrid continuum-particle approach. The cancer cell model includes the cell membrane, nucleus, cytoplasm and the cytoskeleton. The Dissipative Particle Dynamics method was employed to simulate the mechanical components. The blood plasma is modeled as a Newtonian incompressible fluid. A Fluid-Structure Interaction coupling, leveraging the Immersed Boundary Method is developed to simulate the cells response to flow dynamics. We quantify how subtle variations in these biophysical properties alter deformation indices such as sphericity and aspect ratio, and stress distributions on the membrane of the cancer cell. Our findings align well with existing computational and experimental studies. Results reveal that increased membrane stiffness reduces overall deformation as well as the total distance traveled. Similarly, cell geometry strongly influences flow-structure interactions: near-spherical morphologies exhibit stable deformation with minimal sensitivity to shear variations, whereas elongated geometries show pronounced orientation and stretching effects. Collectively, these findings highlight the critical importance of cell-specific heterogeneity in governing cell dynamics in microvascular flows. Furthermore, the intracellular and extracellular dynamics response of the cancer cell are intrinsically linked to their shape, in which certain morphologies displayed strong resistance to the fluid-induced forces and the ability to migrate in various directions. The insights obtained provide a mechanistic framework for understanding circulating tumor cell transport in shear-dominated environments during metastasis. Our work may inform the design of biomimetic microfluidic systems and therapeutic strategies targeting cancer cell detection and cancer prognosis.

biophysics↗

bioRxiv2023

Widespread prevalence of a post-translational modification in activation of an essential bacterial DNA damage response

DNA methylation plays central roles in diverse cellular processes, ranging from error-correction during replication to regulation of bacterial defense mechanisms. Nevertheless, certain aberrant methylation modifications can have lethal consequences. The mechanisms by which bacteria detect and respond to such damage remain incompletely understood. Here, we discover a highly conserved but previously uncharacterized transcription factor (Cada2), which orchestrates a methylation-dependent adaptive response in Caulobacter. This response operates independently of the SOS response, governs the expression of genes crucial for direct repair, and is essential for surviving methylation-induced damage. Our molecular investigation of Cada2 reveals a cysteine methylation-dependent post-translational modification and mode of action distinct from its E. coli counterpart, a trait conserved across all bacteria harboring a Cada2-like homolog instead. Extending across the bacterial kingdom, our findings support the notion of divergence and co-evolution of adaptive response transcription factors and their corresponding sequence-specific DNA motifs. Despite this diversity, the ubiquitous prevalence of adaptive response regulators underscores the significance of a transcriptional switch, mediated by methylation post-translational modification, in driving a specific and essential bacterial DNA damage response.

microbiology↗

bioRxiv2017

SMC Progressively Aligns Chromosomal Arms In Caulobacter crescentus But Is Antagonized By Convergent Transcription

The Structural Maintenance of Chromosomes (SMC) complex plays an important role in chromosome organization and segregation in most living organisms. In Caulobacter crescentus, SMC is required to align the left and the right arms of the chromosome that run in parallel down the long axis of the cell. However, the mechanism of SMC-mediated alignment of chromosomal arms remains elusive. Here, using a genome-wide chromosome conformation capture assay (Hi-C), chromatin immunoprecipitation with deep sequencing (ChIP-seq) and microscopy of single cells, we show that Caulobacter SMC is recruited to the centromeric parS site and that SMC-mediated arm alignment depends on the chromosome partitioning protein ParB. We provide evidence that SMC likely tethers the parS-proximal regions of the chromosomal arms together, promoting arm alignment. Strikingly, the co-orientation of DNA replication and the transcription of highly-expressed genes is crucial for chromosome-wide alignment. Highly-transcribed genes near parS that are oriented against DNA replication disrupt arm alignment suggesting that head-on transcription interferes with SMC translocation and arm alignment. Our results demonstrate a tight interdependence of bacterial chromosome organization and global patterns of transcription.

microbiology↗