Biology subjects

Rahmani, K.

Publications and source records attributed to Rahmani, K..

3 recordsLinked to original sources

bioRxiv2024

Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

Materials with engineered nano-scale surface topographies, such as nanopillars, nanoneedles, and nanowires, mimic natural structures like viral spike proteins, enabling them to bypass biological barriers like the plasma membrane. These properties have led to applications in nanoelectronics for intracellular sensing and drug delivery platforms, some of which are already in clinical trials. Here, we present evidence that nanotopographic materials can induce transient openings in the nuclear membranes of various cell types without penetrating the cells, breaching the nucleo-cytoplasmic barrier and allowing uncontrolled molecular exchange across the nuclear membrane. These openings, induced by nanoscale curvature, are temporary and repaired through ESCRT-mediated mechanisms. Our findings suggest a potential for nano topographic materials for direct nuclear sensing and delivery, holding promise for improving the delivery, efficiency, and safety of therapeutic agents to the nucleus.

bioengineering↗

bioRxiv2024

Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections

Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process. However, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDC or disrupt their interferon production often affect other cells, confounding interpretation. To overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely co-expressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse Cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.

immunology↗

bioRxiv2023

Engineering cell and nuclear morphology on nano topography by contact-free protein micropatterning

Platforms with nanoscale topography have recently become powerful tools in cellular biophysics and bioengineering. Recent studies have shown that nanotopography affects various cellular processes like adhesion and endocytosis, as well as physical properties such as cell shape. To engineer nanopillars more effectively for biomedical applications, it is crucial to gain better control and understanding of how nanopillars affect cell and nuclear physical properties, such as shape and spreading area, and impact cellular processes like endocytosis and adhesion. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate precise engineering of cellular architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, we discovered that cell elongation on nanopillars enhances nanopillar-induced endocytosis. These results have significant implications for various biomedical applications of nanopillars, including drug delivery, drug screening, intracellular electrophysiology, and biosensing. We believe our platform serves as a versatile tool for further explorations, facilitating investigations into the interplay between cell physical properties and alterations in cellular processes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/543791v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1b3a13dorg.highwire.dtl.DTLVardef@1edbdaorg.highwire.dtl.DTLVardef@1f3e40corg.highwire.dtl.DTLVardef@100d6fc_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗