Re-engineering of protein motors to understand mechanisms biasing random motion and generating collective dynamics

https://doi.org/10.1016/j.copbio.2017.11.009Get rights and content

Highlights

  • Protein-based biomolecular motors are remarkable energy transducers.

  • Recent efforts include re-engineering of individual and collective motor functions.

  • Constructive approaches may bring a new perspective on the study of molecular motors.

A considerable amount of insight into the mechanisms of protein-based biomolecular motors has been accumulated over decades of research. However, our knowledge about the design principles of these motors is still limited. Even less is known about the design of multi-motor systems that perform various functions within the cell. Here we focus on constructive (or synthetic) approaches to biomolecular motors that could make a breakthrough in our understanding. Recent achievements include studies at different hierarchical levels of complexity: re-engineering of individual motors, construction of multi-motor systems, and generation of large-scale complex behaviour. We then propose a strategy where the collective behaviour can be repeatedly tested upon modifying individual motors, which may provide important clues about how biomolecular motors and their systems are designed.

Introduction

Since the Industrial Revolution, a variety of machines based on top-down control systems have been made and prevailed in the world. However, these traditional machines, including engines, robots, computers and their networks are showing weaknesses such as difficulty adapting to dramatic changes in the environment. As alternative strategies, increasing attention has been focused on the bottom-up strategies that life adopts.

Section snippets

Autonomous molecular motors that life uses

In living organisms, systems at all levels naturally perform incredibly advanced distributed processing, from the level of ant societies, to individuals, tissues, and down to the cellular level. At the cellular level, the motile machineries such as muscle, mitotic spindle, and cilia/flagella use nanometre-scale molecular machines made of proteins, called biological molecular motors (biomolecular motors), which move along cytoskeletal tracks. These motors capture ATP molecules dissolved in

Key questions in the biomolecular motor field

Remarkably, these tiny machines directly convert chemical energy into directional movement, which makes these motors distinct from man-made macroscopic machines and potentially useful as nanometre-sized actuators [8, 9••]. However, the essential mechanisms that enable such a difficult task is currently unknown. The problem is that biomolecular motors are working in a stochastic environment where the energy of thermal fluctuations is comparable to the energy that can be obtained from ATP

Constructive (synthetic) approaches to biomolecular motors

One effective way to overcome this problem is to take a constructive (or synthetic) approach [11]. The basic idea of the approach is to design (or re-design) and construct new biological components and systems in order to understand life processes. In the case of biomolecular motors, one strategy would be to construct a molecular machine that captures the essence of biomolecular motors. By constructing diverse motile machines that correspond to a single function of directional motility and

Constructing de novo motors

Construction of de novo molecular machines has become a major theme in nanomachine engineering and synthetic biology. In chemistry, three researchers have developed extremely small molecular machines, inspired by biomolecular machines that drive the processes of life. The 2016 Nobel Prize in Chemistry was awarded for their research implementing nanometre scale switches and motors. Switches and motors are similar in that they change their state in response to the environment, but motors

Increasing levels of complexity

Collective behaviour emerging from multi-motor assemblies should be an important step toward understanding the mechanisms generating macroscopic dynamics. A pioneering work [36] engaged many kinesin motors to artificial protein scaffolds with defined motor–motor spacing, and demonstrated that cooperativity among motors can emerge as enhanced ATPase activity and motility. For studying such collective behaviour, the use of DNA-based scaffolds has become more common since the late 2000s. DNA

Toward macroscopic control

In vivo, it is well established that motors and cytoskeletal tracks undergo spontaneous self-assembly into defined structures with surprising accuracy. Yet, a significant knowledge gap exists between the properties of individual molecules and their collective behaviour, which limits our ability to fabricate smart molecules that self-assemble to perform desired functions. To fill this gap, considerable progress has been made through a combination of experimental and theoretical studies [47, 48,

Conclusions

We propose that re-engineering of biomolecular motors might enable us to understand the mechanisms of individual motors and their self-organization. Several hierarchical levels of complexity exist; individual motors themselves consist of polymers that possess numerous internal degrees of freedom, making it difficult to predict the functions from the amino acid sequences. Likewise, networks of molecular motors and cytoskeleton contain complexity with multiple levels of hierarchy that interact

Conflict of interest statement

The authors declare no competing financial interests.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

K. Furuta is supported in part by a Grant-in-Aid for Scientific Research C from the Japan Society for the Promotion of Science (grant number 15KT0155 to K.F.).

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