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The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species. Diverse pathogenic stimuli, including hyperglycemia, dyslipidemia, and inflammation, produce similar reduced protein mobility phenotypes. We propose that proteolethargy is an overlooked cellular mechanism that may account for various pathogenic features of diverse chronic diseases. 

Abstract Incorporating fluorescent quantum defects in the sidewalls of semiconducting single-wall carbon nanotubes (SWCNTs) through chemical reaction is an emerging route to predictably modify nanotube electronic structures and develop advanced photonic functionality. Applications such as room-temperature single-photon emission and high-contrast bio-imaging have been advanced through aryl-functionalized SWCNTs, in which the binding configurations of the aryl group define the energies of the emitting states. However, the chemistry of binding with atomic precision at the single-bond level and tunable control over the binding configurations are yet to be achieved. Here, we explore recently reported photosynthetic protocol and find that it can control chemical binding configurations of quantum defects, which are often referred to as organic color centers, through the spin multiplicity of photoexcited intermediates. Specifically, photoexcited aromatics react with SWCNT sidewalls to undergo a singlet-state pathway in the presence of dissolved oxygen, leading to ortho binding configurations of the aryl group on the nanotube. In contrast, the oxygen-free photoreaction activates previously inaccessible para configurations through a triplet-state mechanism. These experimental results are corroborated by first principles simulations. Such spin-selective photochemistry diversifies SWCNT emission tunability by controlling the morphology of the emitting sites. 

Abstract Insulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced. Treatment of insulin-resistant cells with metformin, a first-line drug used to treat type 2 diabetes, can rescue IR accumulation and the dynamic behavior of these clusters. This rescue is associated with metformin’s role in reducing reactive oxygen species that interfere with normal dynamics. These results indicate that changes in the physico-mechanical features of IR clusters contribute to insulin resistance and have implications for improved therapeutic approaches. 

Conventional molecular recognition elements, such as antibodies, present issues for developing biomolecular assays for use in certain technologies, such as implantable devices. Additionally, antibody development and use, especially for highly multiplexed applications, can be slow and costly. We developed a perception-based platform based on an optical nanosensor array that leverages machine learning algorithms to detect multiple protein biomarkers in biofluids. We demonstrated this platform in gynecologic cancers, often diagnosed at advanced stages, leading to low survival rates. We investigated the detection of protein biomarkers in uterine lavage samples, which are enriched with certain cancer markers compared to blood. We found that the method enables the simultaneous detection of multiple biomarkers in patient samples, with F1-scores of ~0.95 in uterine lavage samples from patients with cancer. This work demonstrates the potential of perception-based systems for the development of multiplexed sensors of disease biomarkers without the need for specific molecular recognition elements. 

The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube–based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high-fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes.