Biology subjects

David, K.

Publications and source records attributed to David, K..

4 recordsLinked to original sources

bioRxiv2026

Label-free Isolation of Heterogeneous Breast Cancer Cell Populations via Insulator-Based Dielectrophoresis

Circulating tumor cells (CTCs) are valuable biomarkers for cancer diagnosis and monitoring, yet their isolation from blood remains challenging due to their phenotypic heterogeneity and rarity. Label-free microfluidic technologies offer a promising alternative to affinity-based approaches by exploiting intrinsic biophysical differences between cell types. Here, we developed a microfluidic platform for label-free cell separation based on insulator-based dielectrophoresis (iDEP). The microfluidic device employs an array of triangular insulating structures that generate strong electric field gradients in response to an externally applied alternating current (AC) electric field, enabling selective isolation of breast cancer cells from blood cells based on their dielectric properties. Hydrodynamic focusing is used to confine the sample stream and precisely control cell trajectories within the separation region. Numerical simulations were performed to optimize the electric field distribution and fluid flow characteristics within the device. Experimental validation using breast cancer cell lines (mesenchymal-like MDA-MB-231 cells and epithelial-like MCF-7 cells) spiked into peripheral blood mononuclear cells (PBMCs) demonstrates selective dielectrophoretic deflection of cancer cells while PBMCs largely follow the central streamline. The platform achieves recovery rates exceeding 98% and a separation purity above 65% within the optimized operating conditions. The proposed system provides a simple label-free approach to separate heterogeneous cell populations and represents a promising tool for microfluidic liquid biopsy enrichment applications.

cancer biology↗

bioRxiv2025

Inter-Spheroid Proximity and Matrix Remodeling Determine CAF-Mediated Cancer Cell Invasion

Breast cancer is the most commonly diagnosed malignancy worldwide, with molecular subtypes following distinct clinical trajectories. While Luminal A breast cancers are typically indolent, a subset enriched in -smooth muscle actin (-SMA)-positive cancer-associated fibroblasts (CAFs) exhibits aggressive behavior, facilitating tumor invasion. However, the biophysical mechanisms by which CAFs drive invasion and extracellular matrix (ECM) remodeling remain unclear. Furthermore, the temporal and spatial dynamics of CAF interactions with the collagen matrix and cancer cell spheroids remain unknown, raising the question of whether these processes follow a deterministic sequence or occur stochastically. To address this, we conduct histological analysis of Luminal A tumors, revealing variation in CAF, cancer cell, and ECM organization at tumor boundaries. To assess the impact of CAF on cancer cell invasion, we use a 3D in-vitro model co-embedding 19TT breast CAF and MCF7 luminal breast cancer spheroids within a three-dimensional (3D) collagen-I hydrogel and perform time-lapse imaging. We demonstrate that inter-spheroid distance critically determines 19TT CAF-induced MCF7 spheroid behavior. Furthermore, we show that CAF-mediated collagen matrix remodeling and degradation precedes MCF7 spheroid disruption and is critical in promoting cancer cell spheroid expansion and cell dissemination. While broad-spectrum matrix metalloproteinase inhibition suppresses CAF-driven collagen degradation and MCF7 spheroid expansion, it does not prevent ECM remodeling, CAF migration, or single-cell dissemination of cancer cell spheroids. Furthermore, a complementary heterospheroid model reveals similar ECM remodeling and invasion dynamics despite altered cellular arrangement of cancer cells and CAFs. These findings enhance our understanding of the relationship between CAF activity and collagen matrix remodeling processes that promote cancer cell invasion, providing insights into the potential therapeutic benefits of targeting CAFs in breast cancer treatment.

cancer biology↗

bioRxiv2023

Multifunctional ferromagnetic fiber robots for navigation, sensing, and treatment in minimally invasive surgery

Small-scale robots capable of remote active steering and navigation offer great potential for biomedical applications. However, the current design and manufacturing procedure impede their miniaturization and integration of various diagnostic and therapeutic functionalities. Here, we present a robotic fiber platform for integrating navigation, sensing, and therapeutic functions at a submillimeter scale. These fiber robots consist of ferromagnetic, electrical, optical, and microfluidic components, fabricated with a thermal drawing process. Under magnetic actuation, they can navigate through complex and constrained environments, such as artificial vessels and brain phantoms. Moreover, we utilize Langendorff mouse hearts model, glioblastoma microplatforms, and in vivo mouse models to demonstrate the capabilities of sensing electrophysiology signals and performing localized treatment. Additionally, we demonstrate that the fiber robots can serve as endoscopes with embedded waveguides. These fiber robots provide a versatile platform for targeted multimodal detection and treatment at hard-to-reach locations in a minimally invasive and remotely controllable manner.

bioengineering↗

bioRxiv2022

Polysome-CAGE of TCL1-driven chronic lymphocytic leukemia revealed multiple N-terminally altered epigenetic regulators and a translation stress signature

The transformation of normal to malignant cells is accompanied by substantial changes in gene expression programs through diverse mechanisms. Here we examined the changes in the landscape of transcription start sites (TSSs) and alternative promoter (AP) usage and their impact on the translatome in TCL1-driven chronic lymphocytic leukemia (CLL). Our findings revealed a marked elevation of APs in CLL cells from E{micro}-Tcl1 transgenic mice, which are particularly enriched with intragenic promoters that generate N-terminally truncated or modified proteins. Intragenic promoter activation is mediated by (i) loss of function of closed chromatin epigenetic regulators due to the generation of inactive N-terminally modified isoforms or reduced expression; (ii) upregulation of transcription factors, including c-Myc, targeting the intragenic promoters and associated enhancers. Exogenous expression of Tcl1 in MEFs is sufficient to induce intragenic promoters of epigenetic regulators and promote c- Myc expression. We further found a dramatic translation downregulation of transcripts bearing CNY cap-proximal tri-nucleotides, reminiscent of cells undergoing metabolic stress. These findings uncovered the role of Tcl1 oncogenic function in altering promoter usage and mRNA translation in leukemogenesis.

molecular biology↗