Protein design studies using coiled coils have illustrated the potential of engineering simple peptides to self-associate into polymers and networks. Although basic aspects of self-assembly in protein systems have been demonstrated, it remains a major challenge to create materials whose large-scale structures are well determined from design of local protein-protein interactions. Here, we show the design and characterization of a helical peptide, which uses phased hydrophobic interactions to drive assembly into nanofilaments and fibrils (''nanoropes''). Using the hydrophobic effect to drive self-assembly circumvents problems of uncontrolled self-assembly seen in previous approaches that used electrostatics as a mode for self-assembly. The nanostructures designed here are characterized by biophysical methods including analytical ultracentrifugation, dynamic light scattering, and circular dichroism to measure their solution properties, and atomic force microscopy to study their behavior on surfaces. Additionally, the assembly of such structures can be predictably regulated by using various environmental factors, such as pH, salt, other molecular crowding reagents, and specifically designed ''capping'' peptides. This ability to regulate self-assembly is a critical feature in creating smart peptide biomaterials.biomaterial ͉ coiled coil ͉ protein design ͉ circular dichroism ͉ atomic force microscopy D esigned proteins are valuable paradigms for engineering at the nanoscale, offering favorable properties such as atomiclevel precision and tight regulation of self-assembly by using a variety of environmental cues (i.e., pH, ionic strength, temperature) (1-3). As one of the most well studied and naturally abundant structural motifs in proteins, coiled coils are particularly suited to protein design. Their basic sequence feature, the heptad repeat, is a seven-residue pattern (abcdefg) n of nonpolar and polar residues that gives rise to amphipathic ␣-helices. The hydrophobic effect drives the burial of nonpolar residues at the helix-pairing interface and influences geometric details of resulting structures (4). Electrostatic and polar residues at buried or solvent-exposed locations provide additional means to manipulate structural features by stabilization or destabilization (negative design) of key interactions (5-8).Recent attempts to design self-assembling protein networks by using coiled coils have focused on simple systems, such as linear and branched fibrils (9-14), planar assemblies (15), and hydrogels (16-18). Specifically, filament formation has been achieved by stabilization of intermediate structures that foster intermolecular coiled-coil interactions (11)(12)(13)(14). Previous studies have reported the design of short helical peptides, which interact via a dimeric coiled-coil motif and are stabilized by a combination of overlapping hydrophobic and electrostatic intermolecular interactions (9, 13, 14). These peptides do indeed self-assemble into filaments; however, these filaments also show evidence of extensive...

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Obesity is an escalating world problem that contributes to the complexity and cost of treatment of metabolic disorders. Obesity is the result of increased storage of energy in the form of adipose tissue, reducing the quality of daily life, and interfering with longevity. Obesity is also a chronic, low-grade inflammatory disorder. The inflammatory processes affect many organ systems with expanded numbers of immune cells and increased cytokine production. Long-term weight loss is difficult to achieve and maintain. Lifestyle modifications, pharmacologic treatments, and surgical methods are increasingly utilized to ameliorate excess body weight and the comorbidities of obesity, such as diabetes, cardiovascular disease, dyslipidemia, and cancers. Weight loss is also touted to reduce inflammation. Here we review the current literature on human obesity-related systemic and local changes to the immune system and circulating inflammatory mediators. Further, we consider the impact of weight loss to reduce the burden of inflammation, bearing in mind the different methods of weight loss—behavioral change vs. surgical intervention. Impact statement As the prevalence and severity of obesity expand, the negative impact of excess adiposity affects every system of the body. Given that obesity is a subversive attack on the immune system, weight loss should improve inflammation locally and systemically. Weight management strategies like dieting, exercise, and bariatric surgery, thus have the opportunity to reduce the burden of inflammation.