Non-specific interactions govern cytosolic diffusion of nanosized objects in mammalian cells

Abstract

The diffusivity of macromolecules in the cytoplasm of eukaryotic cells varies over orders of magnitude and dictates the kinetics of cellular processes. However, a general description that associates the Brownian or anomalous nature of intracellular diffusion to the architectural and biochemical properties of the cytoplasm has not been achieved. Here we measure the mobility of individual fluorescent nanoparticles in living mammalian cells to obtain a comprehensive analysis of cytoplasmic diffusion. We identify a correlation between tracer size, its biochemical nature and its mobility. Inert particles with size equal or below 50 nm behave as Brownian particles diffusing in a medium of low viscosity with negligible effects of molecular crowding. Increasing the strength of non-specific interactions of the nanoparticles within the cytoplasm gradually reduces their mobility and leads to subdiffusive behaviour. These experimental observations and the transition from Brownian to subdiffusive motion can be captured in a minimal phenomenological model.

Zwitterionic polymer ligands: an ideal surface coating to totally suppress protein-nanoparticle corona formation?

“…Nonspecific interactions of nanoparticles with cytoplasmic components is a key determinant for their intracellular dynamics as they lead to sub-diffusive, instead of Brownian motion and reduced mobility. [73] QDs were internalized in the cytoplasm of HeLa cells using electroporation (see Supporting Information) resulting in 10-100 pM intracellular concentrations. The mean square displacements of individual QD trajectories were analyzed to estimate their instantaneous diffusion coefficients (calculated over the first 60 ms) as well as the associated anomalous exponents α (α = 1 for a purely Brownian motion and α < 1 for a sub-diffusive behavior), as shown in Figure 2 (iv) and Table 2.…”

Exfoliated near infrared fluorescent CaCuSi4O10 nanosheets with ultra-high photostability and brightness for biological imaging

“…Active processes and interactions inside the embryo (including movement of the nuclei, contractions and even flow) increase the movement of the nanoprobes beyond diffusion, which can be seen from the increasing slope in the MSD plots ( fig. 5c,d) 47 In the context of biological applications, toxicity is a major concern and for example a potential drawback of quantum dots that contain toxic elements and 2D materials in general 49,50 . To evaluate cytotoxicity, viability assays with EB-NS exposure to different cell lines (A549, 3T3 and MDCK-II) were performed.…”

Statistical Tests for Force Inference in Heterogeneous Environments

“…In the context of biophysics, the random walkers are typically colloidal particles or biomolecules, but, in a general context, they may, for example, represent the motion along an abstract coordinate of a chemical reaction or the fluctuating price of a stock asset. Transport of biomolecules within cells (Wachsmuth et al 2000), conformational dynamics of proteins and RNA molecules (Best and Hummer 2011), diffusion of proteins on the DNA (Vestergaard et al 2018), dynamics of nanosized objects in the cytosol (Etoc et al 2018), dynamics of receptors in neurons (Dahan et al 2003;Choquet 2018;Schneider et al 2015), complex random walks in mixed biological environments (Thapa et al 2018;Grebenkov et al 2018;Javanainen et al 2017;Norregaard et al 2017), bacteria performing chemotaxis (Masson et al 2012;Wong-Ng et al 2016), immune-cell dynamics (Sarris et al 2012;Sarris and Sixt 2015;Fricke et al 2016), and directionally persistent cell movement (Maiuri et al 2015) are all examples of cases where biologically relevant information can be extracted from recorded stochastic trajectories.…”