Abstract
Intermittent transport is frequently observed in nature and has been proven to accelerate search processes at both the macroscopic (e.g., animals looking for food) and microscopic scale (e.g., protein-DNA interactions). In living cells, active transport of membrane proteins (e.g., membrane receptors) or intracellular vesicles (organelles) has been extensively studied as an example of intermittent behavior. The intermittent stochastic process is commonly analyzed in terms of first-passage probabilities. Here we derive exact occupation probabilities of intermittent active transport, making such analysis available for image correlation spectroscopy techniques. The power of this new theoretical framework is demonstrated on intracellular trafficking of lipid/DNA nanoparticles in living cells for which we were allowed to quantify switching time scales.
Highlights
Intermittent mobility and transport, the stop and go movement, is a ubiquitous process that occurs during cargo transport in inhomogeneous media, shuttling proteins in a cell, according to human traffic patterns [1, 2]
It has been argued that in some circumstances, intermittent movement has a distinct advantage in target finding processes that span, on macroscopic scales, from animals and bacteria looking for food [3] to, on the microscopic scale, the transport of vesicles to specific sites [4, 5]
Various motor proteins such as kinesins, dyneins, or myosins are able to convert the chemical fuel provided by adenosine triphosphate (ATP) into mechanical work by interacting with the semiflexible oriented filaments of the cytoskeleton [7]
Summary
Intermittent mobility and transport, the stop and go movement, is a ubiquitous process that occurs during cargo transport in inhomogeneous media, shuttling proteins in a cell, according to human traffic patterns [1, 2]. A particular cellular process that lies at the heart of neurotransmitter transport in axons and the gene delivery by natural and synthetic viruses is that of DNA-filled vesicle transport This transport is characterized by a frequent switching between a passive diffusive mode and an active transport driven by molecular motors [6]. Various experimental strategies have been developed that allow one to study the transport of vesicles in live cells at high spatial and temporal resolution These include the direct visualization by single particle tracking (SPT) [6, 8,9,10,11] and a variety of image correlation spectroscopy (ICS) techniques [12,13,14,15]. This method can highlight the correlation between switching time scales and transfection efficiencies of non-viral nanoparticles made of different lipid formulations
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