Acoustic actuation of bioinspired microswimmers is experimentally demonstrated. Microswimmers are in situ fabricated in a microchannel. Upon acoustic excitation, the flagellum of the microswimmer oscillates, which in turn generates linear or rotary movement depending on the swimmer design. The speed of these bioinspired microswimmers is tuned by adjusting the voltage amplitude applied to the acoustic transducer. Simple microfabrication and remote actuation are promising for biomedical applications.

The appearance of DNA in the cytosol is perceived as a danger signal that stimulates potent immune responses through cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS). How cells regulate the activity of cGAS toward self-DNA and guard against potentially damaging autoinflammatory responses is a fundamental biological question. Here, we identify barrier-to-autointegration factor 1 (BAF) as a natural opponent of cGAS activity on genomic self-DNA. We show that BAF dynamically outcompetes cGAS for DNA binding, hence prohibiting the formation of DNA-cGAS complexes that are essential for enzymatic activity. Upon acute loss of nuclear membrane integrity, BAF is necessary to restrict cGAS activity on exposed DNA. Our observations reveal a safeguard mechanism, distinct from physical separation, by which cells protect themselves against aberrant immune responses toward genomic DNA.

Malignancy and tumour progression are associated with cancer-cell softening. Yet how the biomechanics of cancer cells affects T-cell mediated cytotoxicity and thus the outcomes of adoptive T-cell immunotherapies is unknown. Here, we show that T-cell-mediated cancer-cell killing is hampered for cortically soft cancer cells, whose plasma membrane is enriched with cholesterol, and that cancer-cell stiffening via cholesterol depletion augments T-cell cytotoxicity and enhances the efficacy of adoptive T-cell therapy against solid tumours in mice. We also show that the enhanced cytotoxicity against stiffened cancer cells is mediated by augmented T-cell forces arising from an increased accumulation of filamentous actin at the immunological synapse, and that cancer-cell stiffening has a negligible influence on T-cell-receptor signalling, on the production of cytolytic proteins such as granzyme B, on the secretion of interferon gamma and tumour necrosis factor alpha, and on Fas-receptor–Fas-ligand interactions. Our findings reveal a mechanical immune checkpoint that could be targeted therapeutically to improve the effectiveness of cancer immunotherapies. Cancer cells enriched with cholesterol in their plasma membrane impair T-cell mediated cytotoxicity, which can be augmented by stiffening the cancer cells via cholesterol depletion, as shown in mouse models of adoptive T-cell therapy.

We have demonstrated in situ fabricated and acoustically actuated microrotors. A polymeric microrotor with predefined oscillating sharp-edge structures is fabricated in situ by applying a patterned UV light to polymerize a photocrosslinkable polyethylene glycol solution inside a microchannel around a polydimethylsiloxane axle. To actuate the microrotors by oscillating the sharp-edge structures, we employed piezoelectric transducers which generate tunable acoustic waves. The resulting acoustic streaming flows rotate the microrotors. The rotation rate is tuned by controlling the peak-to-peak voltage applied to the transducer. A 6-arm microrotor can exceed 1200 revolutions per minute. Our technique is an integration of single-step microfabrication, instant assembly around the axle, and easy acoustic actuation for various applications in microfluidics and microelectromechanical systems (MEMS).

Controllable rotational manipulation enables multi-dimensional imaging and rapid screening of single cells and model organisms. Current approaches to rotationally maneuver small objects depend on optical, magnetic, or electrical properties of the sample under investigation. This dependence renders the existing methods sample-specific which limits their applicability. Here we present a new rotational manipulation method based on oscillating sidewall sharp-edge microstructures and thin glass slides in a microchannel. This method is independent of the intrinsic properties of sample under investigation and can be effectively applied to particles, cells, and multicellular organisms.