Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain.

The self-assembly of micellar structures from diblock polymers that contain hydrophilic and hydrophobic domains has been of great interest for the encapsulation of drugs and other hydrophobic molecules. While most commercially used surfactants are derived from hydrocarbon sources, there have been recent efforts to replace these with biodegradable, nontoxic, biologically synthesized alternatives. Previous examples have primarily examined naturally occurring self-assembling proteins, such as silk and elastin-like sequences. Herein, we describe a new series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles that are 27 nm in diameter after enzymatic cleavage of a solubilizing protein tag. The sequences of the proteins are based on a human intrinsically disordered protein, which has been appended with a hydrophobic segment. The micelles were found to form across a broad range of pH, ionic strength, and temperature conditions, with critical micelle concentration (CMC) values in the low micromolar range, 3 orders of magnitude lower than the CMC of commonly used surfactant sodium dodecyl sulfate (SDS). The reported micelles were found to solubilize hydrophobic metal complexes and organic molecules, suggesting their potential suitability for catalysis and drug delivery applications. Furthermore, the inherent flexibility in the design of these protein sequences enables the encoding of additional functionalities for many future applications. Overall, this work represents a new biomolecular alternative to traditional surfactants that are based on nonrenewable and poorly biodegradable hydrocarbon sources.

Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for 'leaky-gut' in inflammatory bowel disease.

Epithelial barrier injury allows contaminants to cross-over into the blood stream and trigger an inflammatory response, contributing to inflammatory bowel disease (IBD). Currently there is no single test that can reliably diagnose intestinal mucosal barrier function or measure impaired epithelial cell integrity associated with increasing permeability. Here, we assess the association between serum proteins and small intestinal permeability as detected by confocal laser endomicroscopy (CLE); in particular the known IBD marker-secreted phosphoprotein 24 (SPP24) and its binding partners; and use developed monoclonal antibodies to assess the role of SPP24 in mucosal healing. Sera were obtained from 28 IBD patients and non-IBD controls undergoing CLE with scores ranging from low to high permeability, as well as active ulcerative colitis from 53 patients undergoing fecal microbiota transplant therapy (FMT). Higher permeability associated with altered lipid metabolism, heightened innate immune response and junctional protein signalling in UC patients. A correlation between increasing leak and SPP24 peptide was observed. There is a strong indication of the novel role of SPP24 in gut barrier dysfunction particularly in ulcerative colitis. Its correlation to the established CLE for monitoring permeability has the potential to provide a blood based parallel to monitor and guide therapy more readily across a broad spectrum of illnesses for which 'leak' dominates the pathology.

Black LGB Identities and Perceptions of Same-Sex Marriage.

The 2015 SCOTUS ruling legalizing same-sex marriage was hailed as a universal victory for the lesbian, gay, and bisexual (LGB) community, but the pervasive support mobilized to achieve this goal may mask important dissension and inequality within the community. Specifically, how race may shape or perpetuate inequalities in the LGB community through same-sex marriage largely has been absent from the discussion. Focusing on the perceived impact of same-sex marriage in respondents' lives, I investigate the relationship between Black LGBs' perception of same-sex marriage legalization and their intersectional identities and community membership. Drawing from the 2010 Social Justice Sexuality Project survey, I explain the complexity of the attitudes of Black LGBs to the legalization of same-sex marriage and illustrate that (1) Black LGBs exhibit heterogeneous interpretation of the effects of same-sex marriage legalization on their lives based on their racial and sexual identities, and (2) same-sex marriage may provide Black LGBs the rationale to affirm their racial community membership as sexual minorities. This study pushes our understanding of the relationship between intersectional identities and individuals' perceptions of the self, identity-based community memberships, and social institutions.