Periodic thermomechanical modulation of toll-like receptor expression and distribution in mesenchymal stromal cells

Xu, Xun; Nie, Yan; Wang, Weiwei; Ma, Nan; Lendlein, Andreas

ABSTRACT: Toll-like receptor (TLR) can trigger an immune response against virus including SARS-CoV-2. TLR expression/distribution is varying in mesenchymal stromal cells (MSCs) depending on their culture environments. Here, to explore the effect of periodic thermomechanical cues on TLRs, thermally controlled shape-memory polymer sheets with programmable actuation capacity were created. The proportion of MSCs expressing SARS-CoV-2-associated TLRs was increased upon stimulation. The TLR4/7 colocalization was promoted and retained in the endoplasmic reticula. The TLR redistribution was driven by myosin-mediated F-actin assembly. These results highlight the potential of boosting the immunity for combating COVID-19 via thermomechanical preconditioning of MSCs. GRAPHIC ABSTRACT: Periodic thermal and synchronous mechanical stimuli provided by polymer sheet actuators selectively promoted the expression of SARS-CoV-2-associated TLRs 4 and 7 in adipose-derived MSCs and recruited TLR4 to Endoplasmic reticulum region where TLR7 was located via controlling myosin-mediated F-actin cytoskeleton assembly. [Image: see text]