Cells bend their plasma membranes into highly curved forms to interact with the local environment, but how shape generation is regulated is not fully resolved. Here, we report a synergy between shape-generating processes in the cell interior and the external organization and composition of the cell-surface glycocalyx. Mucin biopolymers and long-chain polysaccharides within the glycocalyx can generate entropic forces that favor or disfavor the projection of spherical and finger-like extensions from the cell surface. A polymer brush model of the glycocalyx successfully predicts the effects of polymer size and cell-surface density on membrane morphologies. Specific glycocalyx compositions can also induce plasma membrane instabilities to generate more exotic undulating and pearled membrane structures and drive secretion of extracellular vesicles. Together, our results suggest a fundamental role for the glycocalyx in regulating curved membrane features that serve in communication between cells and with the extracellular matrix. (A) The native and synthetic mucin biopolymers that were genetically encoded and used throughout this work. (B) Quantification of membrane tube density in epithelial cells. Mucin polymers induce dramatic tubularization compared to wild-type (Control) cells and compared to a similarly sized biopolymer composed of EGF-like repeats from Notch1 and the Muc1 transmembrane anchor with GFP reporter (EGF-repeats GFP-DCT) cells. Number of cells analyzed is shown on the x axis for each condition. Box notches here and elsewhere indicate 95% confidence intervals. The number of tandem repeats (TRs) are indicated in Muc1 constructs. (C) Scanning electron microscopy (SEM) images of cells expressing the indicated biopolymer. (D) Labelled glycans and membrane morphologies resolved with single-molecule localization microscopy in Muc1-42TR DCT-expressing cells before and after mucin backbone digestion with the StcE mucinase. Images are shown as 2D color-coded histograms of localizations with 32 nm bin width. (E) Representative confocal images of GUVs with and without anchorage of recombinant Podocalyxin. (F) (Left) Cartoons of Muc1 GFP-DCT polymers of varying length. (Right) Flow cytometry data showing similar cell-surface expression levels of the mucins using a GFP-binding nanobody, n = 3, >40,000 cells per population. (G) Representative SEM images of cells expressing mucins with a varying number of TRs. (H) Quantification of membrane tube density for cells expressing the indicated mucins, significance compared to 42TR. ***p < 0.001; ns, not significant (post-hoc Student's two-tailed t test). See also Figure S1.

Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.

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Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

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