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Bourque, A. R.

Publications and source records attributed to Bourque, A. R..

3 recordsLinked to original sources

Integrated Framework for Multiscale Microvascular Models

Microvasculature networks mediate nutrient delivery, waste removal, and drug distribution, yet current microfluidic devices fail to capture biological complexity. Here, we introduce an integrative framework to automate generation of bio-informed microvasculature models unifying in silico and in vitro applications. Our approach leverages a new stochastic growth algorithm governed by fundamental angiogenic principles to generate closed-circuit, fabrication-ready architectures with physiological relevance. We introduce an inverse design strategy that provides a principled mechanism to assign vessel characteristics that satisfy physiological scaling laws. We then present electrical network dynamics, a new algorithm that characterizes network behaviors 100-10,000X faster than CFD, while preserving quantitative predictions. We demonstrate models are fully interchangeable between experimental domains through systematic investigation of vascular topology influence of flow, transport, and cellular behavior. Our platform closes a long-standing gap and provides a generalizable foundation for studying microvascular function in health and disease.

bioengineering↗

Active surface waves drive rippling in Myxococcus xanthus colonies

During periods of predation or starvation, populations of the gliding bacterium Myxococcus xan-thus self-organize into striking wave-like structures termed ripples. This phenomenon was thought to arise from wave collisions triggering synchronized reversals of cell motility. However, using three-dimensional microscopy, we find no evidence for such synchronization during rippling. Instead, we show that ripples are surface waves with a period of [~] 20 min, wavelength of [~] 100 {micro}m and an amplitude of 6 to 20 cell widths at the top of a thick film of cells, akin to surface waves seen in fluids. We propose a physical model of rippling as surface waves of an active nematic liquid crystal. Two key predictions of this model are verified experimentally: the rippling wavelength increases with the surface tension at the film-air interface, and it decreases with substrate stiffness, which regulates the availability of water coating the bacterial film. These findings reveal the physical basis of rippling and highlight the role of active surface waves in shaping collective biological behavior.

biophysics↗

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing

Protein nanoparticles are effective platforms for antigen presentation and targeting effector immune cells in vaccine development. Encapsulins are a class of protein-based microbial nanocompartments that self-assemble into icosahedral structures with external diameters ranging from 24 to 42 nm. Encapsulins from Mxyococcus xanthus were designed to package bacterial RNA when produced in E. coli and were shown to have immunogenic and self-adjuvanting properties enhanced by this RNA. We genetically incorporated a 20-mer peptide derived from a mutant strain of the SARS-CoV-2 receptor binding domain (RBD) into the encapsulin protomeric coat protein for presentation on the exterior surface of the particle. This immunogen elicited conformationally-relevant humoral responses to the SARS-CoV-2 RBD. Immunological recognition was enhanced when the same peptide was presented in a heterologous prime/boost vaccination strategy using the engineered encapsulin and a previously reported variant of the PP7 virus-like particle, leading to the development of a selective antibody response against a SARS-CoV-2 RBD point mutant. While generating epitope-focused antibody responses is an interplay between inherent vaccine properties and B/T cells, here we demonstrate the use of orthogonal nanoparticles to fine-tune the control of epitope focusing. Table of Contents graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/581861v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@53407corg.highwire.dtl.DTLVardef@1ae8d0eorg.highwire.dtl.DTLVardef@aec021org.highwire.dtl.DTLVardef@c7e0ef_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗