The ability to engineer a solvent-exposed surface of self-assembling coiled coils allows one to achieve a higher-order hierarchical assembly such as nano-or microfibers. Currently, these materials are being developed for a range of biomedical applications, including drug delivery systems; however, ways to mechanistically optimize the coiled-coil structure for drug binding are yet to be explored. Our laboratory has previously leveraged the functional properties of the naturally occurring cartilage oligomeric matrix protein coiled coil (C), not only for its favorable motif but also for the presence of a hydrophobic pore to allow for smallmolecule binding. This includes the development of Q, a rationally designed pentameric coiled coil derived from C. Here, we present a small library of protein microfibers derived from the parent sequences of C and Q bearing various electrostatic potentials with the aim to investigate the influence of higher-order assembly and encapsulation of candidate small molecule, curcumin. The supramolecular fiber size appears to be well-controlled by sequence-imbued electrostatic surface potential, and protein stability upon curcumin binding is well correlated to relative structure loss, which can be predicted by in silico docking.

Fluorination represents one of the most powerful modern design strategies to impart biomacromolecules with unique functionality, empowering them for widespread application in the biomedical realm. However, the properties of fluorinated protein materials remain unpredictable due to the heavy context-dependency of the surrounding atoms influenced by fluorine’s strong electron-withdrawing tendencies. This review aims to discern patterns and elucidate design principles governing the biochemical synthesis and rational installation of fluorine into protein and peptide sequences for diverse biomedical applications. Several case studies are presented to deconvolute the overgeneralized fluorous stabilization effect and critically examine the duplicitous nature of the resultant enhanced chemical and thermostability as it applies to use as biomimetic therapeutics, drug delivery vehicles, and bioimaging modalities.

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Gene therapy has the potential to treat various diseases and has recently gained new interest due to the deployment nucleic acid based vaccines for COVID-19. Despite these developments, there still remains a need for further development of gene delivery vehicles to increase their safety and efficacy.. We have recently developed a lipoproteoplex (LPP) consisting of a super-charged coiled-coil protein (CSP) and a cationic liposomal carrier, that has the ability to condense nucleic acids and deliver them in vivo. The LPP is distinct from other liposomal gene delivery systems in that it utilizes a modular protein component to drive transfection activity as opposed to relying on the passive effects of the cationic lipids. A CSP library has been rationally designed to improve the efficacy of the LPP compared to the parent protein via improved alpha-helical structure and increased nucleic acid binding through the use of extended histidine tags and increased positive charge. The secondary structure and nucleic acid binding ability of each library member was assessed, then compared to functional transfection data in NIH-3T3 mouse fibroblasts. Structural and functional data suggests that increasing alpha-helicity of the protein component of the LPP compared to the parent sequence doubles nucleic acid binding affinity and increases transfection activity almost 3-fold with a favorable safety profile.

Entrepreneurial pursuits have historically encountered gender bias in many forms. The stereotypes associated with successful entrepreneurs combined with the upsurge in participation by women in entrepreneurship over recent years have sparked greater interest and research into its gendered differences. Using surveys to gauge the perception of knowledge and experience in entrepreneurship, we assess longitudinally over the last 5 years, differences in responses from men and women in an accelerator program at New York University, dubbed the ‘Startup Sprint’ program. Significant trends in confidence relating to STEM entrepreneurship knowledge and experience are tracked with notably lower average ratings for women. Halfway through the study, the COVID-19 pandemic occurred bringing with it external stressors and a transformation of learning and working environments. Considering the stressors of the COVID-19 pandemic and the transition to a remote educational environment, we analyze our survey results to better understand the impact of these changes on the gendered perceptions of entrepreneurship. Supplementary Information The online version contains supplementary material available at 10.1007/s41959-023-00095-1.

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