Stretchable electronics provide a foundation for applications that exceed the scope of conventional wafer and circuit board technologies due to their unique capacity to integrate with soft materials and curvilinear surfaces. The range of possibilities is predicated on the development of device architectures that simultaneously offer advanced electronic function and compliant mechanics. Here we report that thin films of hard electronic materials patterned in deterministic fractal motifs and bonded to elastomers enable unusual mechanics with important implications in stretchable device design. In particular, we demonstrate the utility of Peano, Greek cross, Vicsek and other fractal constructs to yield space-filling structures of electronic materials, including monocrystalline silicon, for electrophysiological sensors, precision monitors and actuators, and radio frequency antennas. These devices support conformal mounting on the skin and have unique properties such as invisibility under magnetic resonance imaging. The results suggest that fractal-based layouts represent important strategies for hard-soft materials integration.

Thin, soft, and elastic electronics with physical properties well matched to the epidermis can be conformally and robustly integrated with the skin. Materials and optimized designs for such devices are presented for surface electromyography (sEMG). The findings enable sEMG from wide ranging areas of the body. The measurements have quality sufficient for advanced forms of human-machine interface.

Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here we report a skin-like electronics platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of ‘epidermal’ electronics system in a realistic, clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management.

Precision medicine in cancer proposes that genomic characterization of tumors can inform personalized targeted therapies1–5. This proposition, however, is complicated by spatial and temporal heterogeneity6–14. Here we study genomic and expression profiles across 127 multi-sector or longitudinal specimens from 52 glioblastoma (GBM) patients. Using bulk and single-cell data, we find that samples from the same tumor mass share genomic and expression signatures, while geographically separated multifocal tumors and/or long-term recurrent tumors are seeded from different clones. Chemical screening of patient-derived glioma cells (PDCs) shows that therapeutic response is associated to genetic similarity, and multifocal tumors enriched with PIK3CA mutations have a heterogeneous drug response pattern. Importantly, we show that targeting truncal events is more efficacious in reducing tumor burden. In summary, this work demonstrates that evolutionary inference from integrated genomic analysis in multi-sector biopsies can inform targeted therapeutic interventions for GBM patients.

The Met receptor tyrosine kinase, found to be constitutively activated in many tumors, has become a leading target for cancer therapy. Disruptions in Met downregulation have been associated with aggressive tumor progression with several therapeutic strategies addressing this aspect of Met biology. Castias B-lineage lymphoma (Cbl) E3 ligase-mediated degradation, which attenuates Met signaling via ligand-dependent Met internalization, is a major negative regulator of Met expression. It is believed that one of the mechanisms by which the therapeutic anti-Met antibodies induce cancer cell death in Met overexpressing tumors is via internalization and subsequent degradation of Met from the cell surface. However, a previously reported Met-targeting antibody demonstrated intrinsic agonistic activity while being capable of inducing Cbl-mediated degradation of Met, suggesting that Cbl-mediated degradation requires receptor activation and impedes therapeutic application. We have developed a potent and selective bivalent Met-targeting antibody (SAIT301) that invokes Met degradation using an alternative regulator LRIG1. In this report, we demonstrate that LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation. Furthermore, SAIT301 was able to downregulate Met and dramatically inhibit growth of tumors with low or no Cbl expression, as well as tumors with Met exon 14 deletion that prevents Met binding to Cbl. In summary, we demonstrate the enhanced therapeutic potential of a novel tumor-inhibiting anti-Met antibody, SAIT301, which utilizes a Cbl-independent, LRIG1-mediated Met degradation pathway and thereby avoids the agonism that limits the effectiveness of previously reported anti-Met antibodies.

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Our results imply that unique gliomagenesis mechanisms occur in adult cerebellum and new treatment strategies are needed to provide greater therapeutic benefits for C-GBM patients.

Human β-defensin-3 (hBD3) is an endogenous antimicrobial peptide that exhibits broad-spectrum antibacterial activity without eukaryotic cytotoxicity. In this work, we carried out molecular dynamics (MD) simulations to explore its adsorption mechanism on, and the structural and thermodynamic contributions of individual residues to its antibacterial activity with both Gram-negative (GN) and Gram-positive (GP) bacterial membrane. Due to the strong electrostatic interaction of hBD3 with POPG lipids, which are more prevalent on the GP membrane, its adhesion to the GP membrane is stronger than to the GN membrane and stabilized more rapidly. On the surface of both bacterial membranes, the orientation of hBD3 is dominated by an electric dipole. We next analyzed the binding free energy decompositions of the hBD3-membrane complex using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The results of both the GN and the GP membrane simulations show that Arg17, Arg36, and Arg38 form both polar and nonpolar interactions and are potentially the key residues for hBD3 antibacterial activity. On the other hand, there was a significant difference in the energy contribution of Arg12 between the GP and GN membrane simulations, suggesting that Arg12 is a key factor in the toxicity of hBD3 to specifically GP bacteria. Our findings shed light on the antibacterial activity of hBD3 on bacterial membranes and yield insights useful for the design of potent antimicrobial peptides targeting multidrug resistant bacteria.