Laurencikiene, J. | Search bioRxiv

bioRxiv2022

Single particle profiler for measuring properties of nano-sized bioparticles

It is technically challenging to study the content and properties of nanoscale bioparticles in a high-throughput and single-molecule manner. We developed a high-throughput analysis method, called single particle profiler (SPP) that provides single-particle information on content and biophysical properties of thousands of particles. We applied SPP to measure the mRNA encapsulation efficiency of lipid nanoparticles, viral binding efficiency of different nanobodies and biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses.

biophysics↗

bioRxiv2021

Impaired mRNA splicing and proteostasis in preadipocytes in obesity-related metabolic disease

Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we demonstrate that impaired alternative splicing and dysregulated endoplasmic reticulum (ER)- associated protein degradation (ERAD) represent marker pathways of dysfunctional preadipocytes in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). Down-regulation of a key member of the major spliceosome, PRFP8/PRP8, as observed in IR/T2D preadipocytes from subcutaneous (SC) fat, prevented adipogenesis by altering both the expression and splicing patterns of adipogenic transcription factors and lipid droplet-related proteins, while adipocyte differentiation was restored upon recovery of PRFP8/PRP8 normal levels. Adipocyte differentiation was also compromised under conditions of ERAD hyperactivation, as occurs in SC and omental (OM) preadipocytes in IR/T2D obesity. Thus, targeting mRNA splicing and ER proteostasis in preadipocytes could improve adipose tissue function and thus contribute to metabolic health in obese individuals.

cell biology↗