Light-Driven, Dynamic Assembly of Micron-To-Centimeter Parts, Micromachines and Microbot Swarms.

This work describes light-driven assembly of dynamic formations and functional particle swarms controlled by appropriately programmed light patterns. The system capitalizes on the use of a fluidic bed whose low thermal conductivity assures that light-generated heat remains "localized" and sets strong convective flows in the immediate vicinity of the particles being irradiated. In this way, even low-power laser light or light from a desktop slide projector can be used to organize dynamic formations of objects spanning four orders of magnitude in size (from microns to centimeters) and over nine orders of magnitude in terms of mass.

Protocol and Software for Automated Detection of Lysosome Active "Runs" and "Flights" with Wavelet Transform Approach.

Lysosomes are highly dynamic degradation/recycling organelles that harbor sophisticated molecular sensors and signal transduction machinery through which they control cell adaptation to environmental cues and nutrients. The movements of these signaling hubs comprise persistent, directional runs-active, ATP-dependent transport along the microtubule tracks-interspersed by short, passive movements and pauses imposed by cytoplasmic constraints. The trajectories of individual lysosomes are usually obtained by time-lapse imaging of the acidic organelles labeled with LysoTracker dyes or fluorescently-tagged lysosomal-associated membrane proteins LAMP1 and LAMP2.

Large-Scale, Wavelet-Based Analysis of Lysosomal Trajectories and Co-Movements of Lysosomes with Nanoparticle Cargos.

Lysosomes-that is, acidic organelles known for degradation/recycling-move through the cytoplasm alternating between bursts of active transport and short, diffusive motions or even pauses. While their mobility is essential for lysosomes' fusogenic and non-fusogenic interactions with target organelles, their movements have not been characterized in adequate detail. Here, large-scale statistical analysis of lysosomal movement trajectories reveals that lysosome trajectories in all examined cell types-both cancer and noncancerous ones-are superdiffusive and characterized by heavy-tailed distributions of run and flight lengths.

Mixed-Charge Nanocarriers Allow for Selective Targeting of Mitochondria by Otherwise Nonselective Dyes.

Targeted delivery of molecular cargos to specific organelles is of paramount importance for developing precise and effective therapeutics and imaging probes. This work describes a disulfide-based delivery method in which mixed-charged nanoparticles traveling through the endolysosomal tract deliver noncovalently bound dye molecules selectively into mitochondria. This system comprises three elements: (1) The nanoparticles deliver their payloads by a kiss-and-go mechanism - that is, they drop off their dye cargos proximate to mitochondria but do not localize therein; (2) the dye molecules are by themselves nonspecific to any cellular structures but become so with the help of mixed-charge nanocarriers; and (3) the dye is engineered in such a way as to remain in mitochondria for a long time, up to days, allowing for observing dynamic remodeling of mitochondrial networks and long-term tracking of mitochondria even in dividing cells.

Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells.

Lysosomes have become an important target for anticancer therapeutics because lysosomal cell death bypasses the classical caspase-dependent apoptosis pathway, enabling the targeting of apoptosis- and drug-resistant cancers. However, only a few small molecules-mostly repurposed drugs-have been tested so far, and these typically exhibit low cancer selectivity, making them suitable only for combination therapies. Here, we show that mixed-charge nanoparticles covered with certain ratios of positively and negatively charged ligands can selectively target lysosomes in cancerous cells while exhibiting only marginal cytotoxicity towards normal cells.