3. Data modelling, computational biology and predictive medicine, AbstractCells encounter a wide variety of physical and chemical cues when navigating their native environments. However, their response to multiple simultaneous cues is not yet clear. In particular, the influence of topography, in the presence of a chemotactic gradient, on their migratory behavior is understudied. Here, we investigate the effects of topographical guidance on highly motile amoeboid cell migration (topotaxis) generated by asymmetrically placed micropillars. The micropillar field allows for an additional, natural chemotactic gradient in two different directions, thereby revealing the relevance of topotaxis in the presence of cell migration directed by chemical gradients (chemotaxis). Interestingly, we found that the topotactic drift generated by the pillar field is conserved during chemotaxis. We show that the drifts generated by both these cues add up linearly. A coarse-grained analysis as a function of pillar spacing subsequently revealed that the strength and direction of the topotactic drift is determined by (i) the pore size, (ii) space between pores, and (iii) the effective diffusion constant of the cells. Finally, we argue that topotaxis must be conserved during chemotaxis, as it is an emergent property of both the asymmetric properties of the pillar field and the inherent stochasticity of (biased) amoeboid migration.
Many drug delivery systems end up in the lysosome because they are built from covalent or kinetically inert supramolecular bonds. To reach other organelles, nanoparticles hence need to either be made from a kinetically labile interaction that allows re‐assembly of the nanoparticles inside the cell following endocytic uptake, or, be taken up by a mechanism that short‐circuits the classical endocytosis pathway. In this work, the intracellular fate of nanorods that self‐assemble via the Pt…Pt interaction of cyclometalated platinum(II) compounds, is studied. These deep‐red emissive nanostructures (638 nm excitation, ≈700 nm emission) are stabilized by proteins in cell medium. Once in contact with cancer cells, they cross the cell membrane via dynamin‐ and clathrin‐dependent endocytosis. However, time‐dependent confocal colocalization and cellular electron microscopy demonstrate that they directly move to mitochondria without passing by the lysosomes. Altogether, this study suggests that Pt…Pt interaction is strong enough to generate emissive, aggregated nanoparticles inside cells, but labile enough to allow these nanostructures to reach the mitochondria without being trapped in the lysosomes. These findings open new venues to the development of bioimaging nanoplatforms based on the Pt…Pt interaction.
Intracellular transport is pivotal for cell growth and survival. Malfunctions in this process have been associated with devastating neurodegenerative diseases, posing a need for deeper understanding of the involved mechanisms. Here, we used an experimental methodology that lead neurites of differentiated PC12 cells in either of two configurations: an one-dimensional, where the neurites align along lines, or a two-dimensional configuration, where the neurites adopt a random orientation and shape on a flat substrate. We subsequently monitored the motion of functional organelles, the lysosomes, inside the neurites. Implementing a time-resolved analysis of the mean-squared displacement, we quantitatively characterized distinct motion modes of the lysosomes. Our results indicate that neurite alignment gives rise to faster diffusive and super-diffusive lysosomal motion in comparison to the situation where the neurites are randomly oriented. After inducing lysosome swelling through an osmotic challenge by sucrose, we confirmed the predicted slowdown in diffusive mobility. Surprisingly we found that the swelling-induced mobility change affected each of the (sub-/super-) diffusive motion modes differently and depended on the alignment configuration of the neurites. Our findings imply that intracellular transport is significantly and robustly dependent on cell morphology, which might be in part controlled by the extracellular matrix.
In a lot of systems, charge transport is governed by local features rather than being a global property as suggested by extracting a single resistance value. Consequently, techniques that resolve local structure in the electronic potential are crucial for a detailed understanding of electronic transport in realistic devices. Recently, we have introduced a new potentiometry method based on low-energy electron microscopy (LEEM) that utilizes characteristic features in the reflectivity spectra of layered materials [1]. Performing potentiometry experiments in LEEM has the advantage of being fast, offering a large field of view and the option to zoom in and out easily, and of being non-invasive compared to scanning-probe methods. However, not all materials show clear features in their reflectivity spectra. Here we, therefore, focus on a different version of low-energy electron potentiometry (LEEP) that uses the mirror mode transition, i.e. the drop in electron reflectivity around zero electron landing energy when they start to interact with the sample rather than being reflected in front of it. This transition is universal and sensitive to the local electrostatic surface potential (either workfunction or applied potential). It can consequently be used to perform LEEP experiments on a broader range of material compared to the method described in Ref[1]. We provide a detailed description of the experimental setup and demonstrate LEEP on workfunction-related intrinsic potential variations on the Si(111) surface and for a metal-semiconductor-metal junction with external bias applied. In the latter, we visualize the Schottky effect at the metal-semiconductor interface. Finally, we compare how robust the two LEEP techniques discussed above are against image distortions due to sample inhomogeneities or contamination.
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