The advent of molecular tension probes for real-time mapping of piconewton forces in living systems has had a major impact on mechanobiology. For example, DNA-based tension probes have revealed roles for mechanics in platelet, B cell, T cell, and fibroblast function. Nonetheless, imaging short-lived forces transmitted by low-abundance receptors remains a challenge. This is a particular problem for mechanoimmunology where ligand–receptor bindings are short lived, and a few antigens are sufficient for cell triggering. Herein, we present a mechanoselection strategy that uses locking oligonucleotides to preferentially and irreversibly bind DNA probes that are mechanically strained over probes at rest. Thus, infrequent and short-lived mechanical events are tagged. This strategy allows for integration and storage of mechanical information into a map of molecular tension history. Upon addition of unlocking oligonucleotides that drive toehold-mediated strand displacement, the probes reset to the real-time state, thereby erasing stored mechanical information. As a proof of concept, we applied this strategy to study OT-1 T cells, revealing that the T cell receptor (TCR) mechanically samples antigens carrying single amino acid mutations. Such events are not detectable using conventional tension probes. Each mutant peptide ligand displayed a different level of mechanical sampling and spatial scanning by the TCR that strongly correlated with its functional potency. Finally, we show evidence that T cells transmit pN forces through the programmed cell death receptor-1 (PD1), a major target in cancer immunotherapy. We anticipate that mechanical information storage will be broadly useful in studying the mechanobiology of the immune system.
Inspired by biological motor proteins, that efficiently convert chemical fuel to unidirectional motion, there has been considerable interest in developing synthetic analogues. Among the synthetic motors created thus far, DNA motors that undertake discrete steps on RNA tracks have shown the greatest promise. Nonetheless, DNA nanomotors lack intrinsic directionality, are low speed and take a limited number of steps prior to stalling or dissociation. Herein, we report the first example of a highly tunable DNA origami motor that moves linearly over micron distances at an average speed of 40 nm/ min. Importantly, nanomotors move unidirectionally without intervention through an external force field or a patterned track. Because DNA origami enables precise testing of nanoscale structure-function relationships, we were able to experimentally study the role of motor shape, chassis flexibility, leg distribution, and total number of legs in tuning performance. An anisotropic rigid chassis coupled with a high density of legs maximizes nanomotor speed and endurance.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under https://doi.
Engineering free-standing 2D nanomaterials with compositional,
spatial, and functional control across size regimes from the nano-
to mesoscale represents a significant challenge. Herein, we demonstrate
a straightforward strategy for the thermodynamically controlled fabrication
of multicomponent sectored nanosheets in which each sector can be
chemically and spatially addressed independently and orthogonally.
Collagen triple helices, comprising collagen-mimetic peptides (CMPs),
are employed as molecularly programmable crystallizable units. Modulating
their thermodynamic stability affords the controlled synthesis of
2D core–shell nanostructures via thermally driven heteroepitaxial
growth. Structural information, gathered from SAXS and cryo-TEM, reveals
that the distinct peptide domains maintain their intrinsic lattice
structure and illuminates various mechanisms employed by CMP triple
helices to alleviate the elastic strain associated with the interfacial
lattice mismatch. Finally, we demonstrate that different sectors of
the sheet surface can be selectively functionalized using bioorthogonal
conjugation chemistry. Altogether, we establish a robust platform
for constructing multifunctional 2D nanoarchitectures in which one
can systematically program their compositional, spatial, and functional
properties, which is a significant step toward their deployment into
functional nanoscale devices.
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