Crowding-facilitated macromolecular transport in attractive micropost arrays

Fan-Tso Chien,Po-Keng Lin,Yeng-Long Chen,Ming-Hung Yu,Wei Chien,Chia-Fu Chou,Cheng-Hsiang Hung

doi:10.1038/s41598-017-01248-8

Abstract

Our study of DNA dynamics in weakly attractive nanofabricated post arrays revealed crowding enhances polymer transport, contrary to hindered transport in repulsive medium. The coupling of DNA diffusion and adsorption to the microposts results in more frequent cross-post hopping and increased long-term diffusivity with increased crowding density. We performed Langevin dynamics simulations and found maximum long-term diffusivity in post arrays with gap sizes comparable to the polymer radius of gyration. We found that macromolecular transport in weakly attractive post arrays is faster than in non-attractive dense medium. Furthermore, we employed hidden Markov analysis to determine the transition of macromolecular adsorption-desorption on posts and hopping between posts. The apparent free energy barriers are comparable to theoretical estimates determined from polymer conformational fluctuations.

Highlights

Efficient transport of large particles and molecules in crowded environments is essential for biological processes in cells[1, 2] and for molecular separation[3, 4]
Our observations of DNA motion in nanoslit micropost arrays revealed that DNA COM trajectories undergo apparent “hopping” motions due to large conformation fluctuations and segmental adsorption/ desorption to the micropost array
The “hopping” process is uniquely due to large conformational fluctuations accessibly with DNA molecules and large floppy macromolecules, in contrast to the adsorption/desorption of small compact macromolecules from charged patches at a liquid-solid interface[30,31,32,33,34,35]

Summary

Introduction

Efficient transport of large particles and molecules in crowded environments is essential for biological processes in cells[1, 2] and for molecular separation[3, 4]. A very recent model showed that increased crowding density could facilitate macromolecular transport in a micropost array that attracts macromolecules[11] In complex environments such as within a living cell, a macromolecule could interact with organelles, proteins, and the cytoskeletal network, and its transport dynamics is more complex. In the nanoslit micropost array device, DNA molecules appeared to weakly absorb to the posts, fluctuate in conformation and “hop” across different posts under no external fields[17, 20] This “hopping” motion may be coupled to rare large DNA conformation fluctuations that occur in a very short time frame, limitations in observation sampling frequencies does not allow us to resolve the process. With the ability to take images only at fixed time intervals that may be longer than needed to capture very short-lived large conformation fluctuation events, we developed a hidden Markov model to determine the hopping probability from DNA trajectories and to infer the energy landscape in this crowded environment[5, 23]

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Conclusion