Synthetic biology approaches to dissecting linear motor protein function: towards the design and synthesis of artificial autonomous protein walkers

Abstract

Molecular motors and machines are essential for all cellular processes that together enable life. Built from proteins with a wide range of properties, functionalities and performance characteristics, biological motors perform complex tasks and can transduce chemical energy into mechanical work more efficiently than human-made combustion engines. Sophisticated studies of biological protein motors have provided many structural and biophysical insights and enabled the development of models for motor function. However, from the study of highly evolved, biological motors, it remains difficult to discern detailed mechanisms, for example, about the relative role of different force generation mechanisms, or how information is communicated across a protein to achieve the necessary coordination. A promising, complementary approach to answering these questions is to build synthetic protein motors from the bottom up. Indeed, much effort has been invested in functional protein design, but so far, the "holy grail" of designing and building a functional synthetic protein motor has not been realized. Here, we review the progress made to date, and we put forward a roadmap for achieving the aim of constructing the first artificial, autonomously running protein motor. Specifically, we propose to break down the task into (i) enzymatic control of track binding, (ii) the engineering of asymmetry and (iii) the engineering of allosteric control for internal communication. We also propose specific approaches for solving each of these challenges.

Biophysical Reviews: 2020—looking back, going forward

“…The bulk of the scientific content of this Issue was constituted by twenty-two topical review articles that spanned different areas of cardiac research. Some particularly noteworthy examples dealt with growth factor directed therapy for cardiac muscle repair (White and Chong 2020 ); cardiomyocyte fluoresce-based microscopy methods (Janco et al 2020 ; Pandzic et al 2020 ; Hassan et al 2020 ); cellular mechano-transduction and shape determinants on cell growth regulation (Esfahani and Knöll 2020 ; Pruna and Ehler 2020 ; Harley et al 2020 ); synthetic biology approaches to the study of motor proteins (Linke et al 2020 ); use of plasma technology in surgical equipment surface treatment (Harley et al 2020 ); and the regulatory pathways and structural roles of profilin (Davey and Moens 2020 ).…”

Harvesting information to control non-equilibrium states of active matter

“…Our result makes explicit the deep connection between information and non-equilibrium thermodynamics, which is central to molecular motors and living systems capable of extracting energy from their fluctuating environments to accelerate their average motion, e.g. [21][22][23].…”

Modeling myosin with interacting linkages

“…Biomolecular motors convert chemical energy into directed motion at the nanoscale. Replicating this capability in synthetic systems is a long-term goal of engineers [1,2]. To achieve this goal, the mechanisms that allow molecular motors to function must be translated into buildable concepts which researchers can ideally apply to more than one kind of chemistry [2,3].…”

“…In nanotechnology there is a long-term goal of constructing chemically-fuelled and autonomous molecular machines that actively transport small molecules over nanoscale distances [1, 2]. Inspiration for these machines comes directly from nature, where biomolecular motors and pumps play a central role in maintaining cellular activity through a variety of tasks.…”