Exploiting mammalian low-complexity domains for liquid-liquid phase separation–driven underwater adhesive coatings

Abstract

Many biological materials form via liquid-liquid phase separation (LLPS), followed by maturation into a solid-like state. Here, using a biologically inspired assembly mechanism designed to recapitulate these sequential assemblies, we develop ultrastrong underwater adhesives made from engineered proteins containing mammalian low-complexity (LC) domains. We show that LC domain–mediated LLPS and maturation substantially promotes the wetting, adsorption, priming, and formation of dense, uniform amyloid nanofiber coatings on diverse surfaces (e.g., Teflon), and even penetrating difficult-to-access locations such as the interiors of microfluidic devices. Notably, these coatings can be deposited on substrates over a broad range of pH values (3 to 11) and salt concentrations (up to 1 M NaCl) and exhibit strong underwater adhesion performance. Beyond demonstrating the utility of mammalian LC domains for driving LLPS in soft materials applications, our study illustrates a powerful example of how combining LLPS with subsequent maturation steps can be harnessed for engineering protein-based materials.

Biological phase separation: cell biology meets biophysics

“…AFM surveys the structure of a protein weakly immobilized onto a sample stage substrate by tapping the protein using a cantilever (Ando et al 2013). High-speed AFM provides real-time video of the protein in solution at nm-resolution on the second or sub-second timescale, and has been used to investigate the polymers of LC proteins (Babinchak et al 2019) and gels of protein fibers (Cui et al 2019;Wang et al 2019). More recently, high-speed AFM has been utilized in the observation of the protein in the LLPS droplet (Fujioka et al 2020).…”

The Different Faces of the TDP-43 Low-Complexity Domain: The Formation of Liquid Droplets and Amyloid Fibrils

“…Moreover, acetylation and methylation can also affect the cation–π or charge–charge interactions to modulate LLPS [ 57 , 58 , 59 ]. Although the components within these liquid droplets in vivo are complicated, proteins with LCDs, TDP-43 included, were extensively found within, implying LCDs play an essential role in mediating droplet formation [ 27 , 28 , 48 , 60 , 61 , 62 ].…”

Self-assembled fibrinogen–fibronectin hybrid protein nanofibers with medium-sensitive stability

“…Protein nanobers (PNFs) are a subject of current research in the eld of interdisciplinary nanoscience due to their unique properties, such as good biocompatibility, large surface area, as well as their ability to mimic individual structures of naturally occurring tissue. [1][2][3][4][5][6][7][8][9] On account of the growing area of tissue engineering, several approaches to create PNFs have been introduced over the past years, including electrospinning, 2,3,7,10 phase separation, 11,12 and extrusion. 4,9,[12][13][14] These approaches allow the creation of nanobers with uniform dimensions, i.e., diameter and length, yet with limited functionalities and consequently a narrow application range.…”