Biology subjects

Lisse, D.

Publications and source records attributed to Lisse, D..

2 recordsLinked to original sources

bioRxiv2024

Live-cell magnetic micromanipulation of recycling endosomes reveals their direct effect on actin-based protrusions to promote invasive migration

Endocytic recycling pathways play key roles in the re-routing of cargoes through the cell to control a broad range of cellular processes, and many vesicle trafficking regulators are implicated in progression of disease such as cancer. The Rab11 family (Rab11a, Rab11b, and Rab25) control return of internalised cargoes to the plasma membrane, and Rab25 has been implicated in the aggressiveness of cancer by promoting invasive migration. However, whilst Rab25 vesicles distribute to the leading of edge of moving cells, how directly they contribute to cell protrusion is not clear. Here we adopt a magnetogenetic approach that allows direct manipulation of Rab25 positioning to show that localisation to the cell periphery drives the formation of F-actin protrusions. We demonstrate that endogenous Rab25 vesicles coordinate the positioning of key cargoes, including the actin regulator FMNL1 and integrin {beta}1, with the activation of Rho GTPases at the plasma membrane to generate and maintain F-actin rich filopodial protrusions and promote cancer cell invasive migration in 3D matrix.

cancer biology↗

bioRxiv2024

Biofunctional coating of synthetic magnetic nanoparticles enables magnetogenetic control of protein functions inside cells

Remote control of cellular functions via magnetic forces offers unique opportunities in fundamental research and biomedical application. Intracellular delivery of functionalized magnetic nanoparticles (MNP) provides versatile opportunities to assemble signalling platforms for spatiotemporal control by magnetic forces. Such magnetogenetic application, however, has remained highly challenging due to a lack of MNP providing suitable biological, physicochemical and magnetic properties. Here, we achieved single-step surface coating of synthetic maghemite core nanoparticles with green fluo-rescent protein fused to the iron binding site of Mms6 from magnetotactic bacteria. We yielded MNP with intracellular stealth properties (syMagIcS), which could be readily biofunctionalized in situ and translocated within cells via magnetic field gradients. We successfully exploited syMagIcS for spati-otemporal control of Rac1 signalling at the plasma membrane via its guanine nucleotide exchange factor protein TIAM1 and for spatial control of liquid-liquid phase separation using the intrinsically disordered domain of the protein DDX4.

biophysics↗