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Triplet–triplet annihilation upconversion (TTA-UC) is a process that shows promise for applications such as energy-harvesting and light-generation technologies. The irradiance dependent performance of TTA-UC systems is typically gauged using a graphical analysis, rather than a detailed model. Additionally, kinetic models for TTA-UC rarely incorporate mass conservation, which is a phenomenon that can have important consequences under experimentally relevant conditions. We present an analytical, mass-conserving kinetic model for TTA-UC, and demonstrate that the mass-conservation constraint cannot generally be ignored. This model accounts for saturation in TTA-UC data. Saturation complicates the interpretation of the threshold irradiance I th , a popular performance metric. We propose two alternative figures of merit for overall performance. Finally, we show that our model can robustly fit experimental data from a wide variety of sensitized TTA-UC systems, enabling the direct and accurate determination of I th and of our proposed performance metrics. We employ this fitting procedure to benchmark and compare these metrics, using data from the literature. 

Abstract Asymmetric nanotopography with sub-cellular dimensions has recently demonstrated the ability to provide a unidirectional bias in cell migration. The details of this guidance depend on the type of cell studied and the design of the nanotopography. This behavior is not yet well understood, so there is a need for a predictive description of cell migration on such nanotopography that captures both the initiation of migration, and the way cell migration evolves. Here, we employ a three-dimensional, physics-based model to study cell guidance on asymmetric nanosawteeth. In agreement with experimental data, our model predicts that asymmetric sawteeth lead to spontaneous motion. Our model demonstrates that the nanosawteeth induce a unidirectional bias in guidance direction that is dependent upon actin polymerization rate and sawtooth dimensions. Motivated by this model, an analysis of previously reported experimental data indicates that the degree of guidance by asymmetric nanosawteeth increases with the cell velocity. 

Contact guidance is a powerful topographical cue that induces persistent directional cell migration. Healthy tissue stroma is characterized by a meshwork of wavy extracellular matrix (ECM) fiber bundles, whereas metastasis-prone stroma exhibit less wavy, more linear fibers. The latter topography correlates with poor prognosis, whereas more wavy bundles correlate with benign tumors. We designed nanotopographic ECM-coated substrates that mimic collagen fibril waveforms seen in tumors and healthy tissues to determine how these nanotopographies may regulate cancer cell polarization and migration machineries. Cell polarization and directional migration were inhibited by fibril-like wave substrates above a threshold amplitude. Although polarity signals and actin nucleation factors were required for polarization and migration on low-amplitude wave substrates, they did not localize to cell leading edges. Instead, these factors localized to wave peaks, creating multiple “cryptic leading edges” within cells. On high-amplitude wave substrates, retrograde flow from large cryptic leading edges depolarized stress fibers and focal adhesions and inhibited cell migration. On low-amplitude wave substrates, actomyosin contractility overrode the small cryptic leading edges and drove stress fiber and focal adhesion orientation along the wave axis to mediate directional migration. Cancer cells of different intrinsic contractility depolarized at different wave amplitudes, and cell polarization response to wavy substrates could be tuned by manipulating contractility. We propose that ECM fibril waveforms with sufficiently high amplitude around tumors may serve as “cell polarization barriers,” decreasing directional migration of tumor cells, which could be overcome by up-regulation of tumor cell contractility.

 

The dynamic rearrangement of the actin cytoskeleton is an essential component of many mechanotransduction and cellular force generation pathways. Here we use periodic surface topographies with feature sizes comparable to those of in vivo collagen fibers to measure and compare actin dynamics for two representative cell types that have markedly different migratory modes and physiological purposes: slowly migrating epithelial MCF10A cells and polarizing, fast-migrating, neutrophil-like HL60 cells. Both cell types exhibit reproducible guidance of actin waves (esotaxis) on these topographies, enabling quantitative comparisons of actin dynamics. We adapt a computer-vision algorithm, optical flow, to measure the directions of actin waves at the submicron scale. Clustering the optical flow into regions that move in similar directions enables micron-scale measurements of actin-wave speed and direction. Although the speed and morphology of actin waves differ between MCF10A and HL60 cells, the underlying actin guidance by nanotopography is similar in both cell types at the micron and submicron scales.