Biology subjects

Radiom, M.

Publications and source records attributed to Radiom, M..

3 recordsLinked to original sources

bioRxiv2023

Surface crosslinking of virus-like particles increases resistance to proteases, low pH and mechanical stress for mucosal applications

AbstractVirus-like particles (VLPs) are emerging as nano-scaffolds in a variety of biomedical applications including the delivery of vaccine antigens to mucosal surfaces. These soft, colloidal, and proteinaceous structures (capsids) are nevertheless susceptible to mucosal environmental factors which limit their usefulness. We addressed this issue by crosslinking multiple capsid surface reactive residues using polyethylene glycol tethers. Surface crosslinking enhanced the colloidal stability and mechanical strength of VLPs against low pH, proteases, and mechanical agitation, while it did not interfere with function as vaccine. Chemical crosslinking thus offers a viable means to enhance the resilience of VLPs in mucosal applications.

biophysics↗

bioRxiv2023

Nanoscale clustering by O-antigen-Secretory Immunoglobulin-A binding limits outer membrane diffusion by encaging individual Salmonella cells

Secreted immunoglobulins, predominantly SIgA, influence the colonization and pathogenicity of mucosal bacteria. While part of this effect can be explained by SIgA-mediated bacterial aggregation, we have an incomplete picture of how SIgA binding influences cells independently of aggregation. Here we show that akin to microscale crosslinking of cells, SIgA targeting the Salmonella Typhimurium O-antigen extensively crosslinks the O-antigens on the surface of individual bacterial cells at the nanoscale. This crosslinking results in an essentially immobilized bacterial outer membrane. Membrane immobilization, combined with Bam-complex mediated outer membrane protein insertion results in biased inheritance of IgA-bound O-antigen, concentrating SIgA-bound O-antigen at the oldest poles during cell growth. By combining empirical measurements and simulations, we show that this SIgA-driven biased inheritance increases the rate at which phase-varied daughter cells become IgA-free: a process that can accelerate IgA escape via phase-variation of O-antigen structure. Our results show that O-antigen-crosslinking by SIgA impacts workings of the bacterial outer membrane, helping to mechanistically explain how SIgA may exert aggregation-independent effects on individual microbes colonizing the mucosae.

microbiology↗

bioRxiv2021

Magnetic wire active microrhreology of human respiratory mucus

Mucus is a viscoelastic gel secreted by the pulmonary epithelium in the tracheobronchial region of the lungs. The coordinated beating of cilia in contact with the gel layer moves mucus upwards towards pharynx, removing inhaled pathogens and particles from the airways. The efficacy of this clearance mechanism depends primarily on the rheological properties of mucus. Here we use a magnetic wire based microrheology technique to study the viscoelastic properties of human mucus collected from human bronchus tubes. The response of wires between 5 and 80 {micro}m in length to a magnetic rotating field is monitored by optical time-lapse microscopy and analyzed using constitutive equation models of rheology, including Maxwell and Kelvin-Voigt. The static shear viscosity and elastic modulus can be inferred from low frequency (10-3 - 10 rad s-1) measurements, leading to the evaluation of the mucin network relaxation time. This relaxation time is found to be widely distributed, from one to several hundred seconds. Mucus is identified as a viscoelastic liquid with an elastic modulus of 2.5 {+/-} 0.5 Pa and a static viscosity of 100 {+/-} 40 Pa s. Our work shows that beyond the established spatial variations in rheological properties due to microcavities, mucus exhibits secondary inhomogeneities associated with the relaxation time of the mucin network that may be important for its flow properties.

biophysics↗