Biology subjects

Kruse, L. E.

Publications and source records attributed to Kruse, L. E..

3 recordsLinked to original sources

bioRxiv2024

Generalization of the Packing Parameter for Quantifying the Morphology of Peptide Amphiphile Micelles

We present a quantitative means for classifying the shape of molecular dynamics simulated peptide amphiphile micelles (PAMs) that is both consistent with existing metrics and extendable to estimating shape-dependent free energy contributions. The presented framework not only outlines an approach for characterizing the shape of simulated PAMs but also presents expressions that can readily be applied to quantify the shape of particles from experimental techniques where aspect ratios are measured. The generalization of the packing parameter introduces a characteristic length that, when applied to simulated PAMs, functions intuitively as an effective radius for a PAM whose core is a perfect sphere or an infinite cylinder. The presented shape assignment scheme is used to develop a model for the free energy penalty associated with packing the tails of the amphiphiles into a core whose shape is modeled by an ellipsoid. Good agreement with previous models and scaling behaviors is observed and the importance of accounting for the shape and size dependence of the core is illustrated. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/598326v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1b326d4org.highwire.dtl.DTLVardef@ba5e82org.highwire.dtl.DTLVardef@192e29forg.highwire.dtl.DTLVardef@5c63b1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Adjuvant Delivery Method and Nanoparticle Charge Influence Peptide Amphiphile Micelle Vaccine Bioactivity

Vaccines are an indispensable public health measure that have enabled the eradication, near elimination, and prevention of a variety of pathogens. As research continues and our understanding of immunization strategies develops, subunit vaccines have emerged as exciting alternatives to existing whole vaccine approaches. Unfortunately, subunit vaccines often possess weak antigenicity, requiring delivery devices and adjuvant supplementation to improve their utility. Peptide amphiphile micelles have recently been shown to function as both delivery devices and self-adjuvanting systems that can be readily associated with molecular adjuvants to further improve vaccine-mediated host immunity. While promising, many "design rules" associated with the plethora of underlying adjustable parameters in the generation of a peptide amphiphile micelle vaccine have yet to be uncovered. This work explores the impact micellar adjuvant complexation method and incorporated antigen type have on their ability to activate dendritic cells and induce antigen specific responses. Interestingly, electrostatic complexation of CpG to micelles resulted in improved in vitro dendritic cell activation over hydrophobic association and antigen|adjuvant co-localization influenced cell-mediated, but not antibody-mediated immune responses. These exciting results complement those previously published to build the framework of a micelle vaccine toolbox that can be leveraged for future disease-specific formulations.

bioengineering↗

bioRxiv2024

Vasoactive Intestinal Peptide Amphiphile Micelle Material Properties Influence Their Cell Association and Internalization

Vasoactive intestinal peptide (VIP) is a promising anti-inflammatory peptide therapeutic that is known to induce biological effects by interacting with its cognate receptor (i.e., VPAC) on the surface of antigen presenting cells (APCs). For VIP-based drug delivery technologies like nano- and microparticles, little is known about the effect VPAC targeting has on APC behavior. This is further influenced by the fact that particulate material properties including chemistry, shape, and size are all known to influence APC behavior. In this study, peptide amphiphile micelles (PAMs) were employed as a modifiable platform to study the impact VPAC targeting and physical particle properties have on their association with macrophages. VIP amphiphile micelles (VIPAMs) and their scrambled peptide amphiphile micelle analogs (SVIPAMs) were fabricated from various chemistries yielding particle batches that were comprised of spheres (10 - 20 nm in diameter) and/or cylinders of varying lengths (i.e., 20 - 9000 nm). Micelle surface attachment to and internalization by macrophages were observed using confocal microscopy and their association was characterized by flow cytometry. The enclosed work provides strong evidence that macrophages rapidly bind VPAC specific micelles independent of physical properties though micelle shape and size as well as receptor-specificity all influence their long-term macrophage association. Specifically, a mixture of spherical and short cylindrical VIPAMs were able to achieve the greatest cell association which may correlate to their capacity to fully bind the VPAC receptors available on the surface of macrophages. These results provide the foundation of how nano- and microparticle physical properties and targeting capacity synergistically influence their capacity to associate with APCs.

bioengineering↗