Powering Motion with Enzymes

Xi Zhao, Kayla Gentile, Farzad Mohajerani, Ayusman Sen

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

ConspectusEnzymes are ubiquitous in living systems. Apart from traditional motor proteins, the function of enzymes was assumed to be confined to the promotion of biochemical reactions. Recent work shows that free swimming enzymes, when catalyzing reactions, generate enough mechanical force to cause their own movement, typically observed as substrate-concentration-dependent enhanced diffusion. Preliminary indication is that the impulsive force generated per turnover is comparable to the force produced by motor proteins and is within the range to activate biological adhesion molecules responsible for mechanosensation by cells, making force generation by enzymatic catalysis a novel mechanobiology-relevant event. Furthermore, when exposed to a gradient in substrate concentration, enzymes move up the gradient: an example of chemotaxis at the molecular level. The driving force for molecular chemotaxis appears to be the lowering of chemical potential due to thermodynamically favorable enzyme-substrate interactions and we suggest that chemotaxis promotes enzymatic catalysis by directing the motion of the catalyst and substrates toward each other.Enzymes that are part of a reaction cascade have been shown to assemble through sequential chemotaxis; each enzyme follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Thus, sequential chemotaxis in catalytic cascades allows time-dependent, self-assembly of specific catalyst particles. This is an example of how information can arise from chemical gradients, and it is tempting to suggest that similar mechanisms underlie the organization of living systems. On a practical level, chemotaxis can be used to separate out active catalysts from their less active or inactive counterparts in the presence of their respective substrates and should, therefore, find wide applicability. When attached to bigger particles, enzyme ensembles act as "engines", imparting motility to the particles and moving them directionally in a substrate gradient. The impulsive force generated by enzyme catalysis can also be transmitted to the surrounding fluid and molecular and colloidal tracers, resulting in convective fluid pumping and enhanced tracer diffusion. Enzyme-powered pumps that transport fluid directionally can be fabricated by anchoring enzymes onto a solid support and supplying the substrate. Thus, enzyme pumps constitute a novel platform that combines sensing and microfluidic pumping into a single self-powered microdevice. Taken in its entirety, force generation by active enzymes has potential applications ranging from nanomachinery, nanoscale assembly, cargo transport, drug delivery, micro- and nanofluidics, and chemical/biochemical sensing. We also hypothesize that, in vivo, enzymes may be responsible for the stochastic motion of the cytoplasm, the organization of metabolons and signaling complexes, and the convective transport of fluid in cells. A detailed understanding of how enzymes convert chemical energy to directional mechanical force can lead us to the basic principles of fabrication, development, and monitoring of biological and biomimetic molecular machines.

Original languageEnglish (US)
Pages (from-to)2373-2381
Number of pages9
JournalAccounts of Chemical Research
Volume51
Issue number10
DOIs
StatePublished - Oct 16 2018

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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