Biomolecular motors exhibit outstanding functions, including efficient motion and force generation, as well as autonomous operation. In this Essay, I discuss how biomolecular motors can be engineered to be used in artificial systems and what future applications such systems might have.

In recent years, we have envisioned a society in which everything in the environment is connected to a network, as described by concepts such as the ‘internet of things’ (IoT). The IoT consists of physical objects – including toothbrushes, keys, cameras, refrigerators, lighting, cars and even humans (via wearable technology and implants) – that are connected via communications networks to improve the efficiency and safety of our daily lives. However, what kind of future would await us if such a society was built as a centralized system with a command centre? No software, no matter how carefully designed, is perfect, and as has often been reported in the news, a small error can lead to a major system failure. Besides, if such a system is based on electricity-driven silicon devices, energy shortages are sure to be a problem for the reliable operation of countless devices.

Awareness of these issues has led to an increasing interest in exploiting the strategies employed by living organisms for computing applications. In biological systems, a distributed control is somehow achieved by numerous cells communicating with each other at the local level, while making use of only the energy available in the environment. Putting these capabilities into writing in this Essay, I once again appreciate the ‘magic’ that cells use to achieve these amazing functions. The cell has many types of nanomachines, and it is obvious that their orchestration plays an indispensable role in its proper functioning.

Among the nanomachines used in cells, biomolecular motors are machines that convert chemical energy into mechanical energy with high efficiency, and they perform a wide variety of tasks inside the cell. Among those, linear biomolecular motors – such as myosins, kinesins and dyneins – are machines that move on the cytoskeleton, thereby driving processes such as muscle contraction, cell division and flagellar beating.

For decades, biologists have been trying to apply biomolecular motors to devices (van den Heuvel and Dekker, 2007), including microscale actuators that generate motion and forces (Nitta et al., 2021), as well as molecular computing devices (Nicolau et al., 2016). One of the barriers to these motor applications is the dynamic nature of the cytoskeleton. The cytoskeleton undergoes dynamic morphological changes, which perform important functions within the cell. However, this dynamic nature makes it very difficult to intervene in or control motor function. Therefore, the use of DNA tracks, whose structure and arrangements can be precisely controlled, for motors to move on has been considered. Since the 2000s, DNA nanotechnology has emerged, which offers the use of DNA not as genetic information but as an extremely small building material to design and fabricate desired structures, including sheets, tubes, cubes, smiley faces and so forth (Seeman, 2010; Rothemund, 2006). However, it has not been possible to create machines that can move quickly and autonomously on DNA tracks. This is mainly because such a tiny machine is exposed to intense noise due to the thermal agitation of surrounding molecules. To control such machines with the existing technology, it is necessary to provide an external source of energy to overwhelm the thermal noise. Natural biomolecular motors moving on cytoskeletal tracks are also exposed to thermal agitation, but they seem to deal with thermal noise through clever mechanisms that we do not yet fully understand.

As a result, attention has focused on biomolecular motors that can move autonomously by providing them with only 20 times more energy than the thermal noise. In 2022, my group developed a chimeric motor, fusing a naturally occurring DNA-binding protein (for example, LEF1 or σA4) with a dynein motor (Ibusuki et al., 2022). This hybrid motor walks on an artificial DNA track at speeds comparable to those of biomolecular motors inside cells and navigates according to programs written in the DNA sequence. For example, the hybrid motors move according to cues such as ‘go right’ or ‘go left’ that are embedded in a Y-shaped track, leading to a molecular transport system that sorts cargoes on a nanometre scale. Moreover, the self-assembly capability with high reproducibility and controllability of DNA nanostructures makes robotics applications of molecular motors more realistic. By packing and arranging many motors on DNA nanostructures, the resultant assembly would generate large forces with low energy consumption, just as muscles and flagella naturally do.

Apart from actuation – the control of motion and generation of forces – information processing is another key function of biological systems. The original purpose of DNA in cells is to carry genetic information, which acts as sort of a program code to instruct cells how to develop and function. We can ‘hack’ this code by embedding information into DNA tracks that instructs motors not only where to move and what to transport, but also what to activate or even synthesize – the hybrid motors could activate key molecules that are placed near the end of the track or could link together the monomers of a polymer, such as a peptide, while reading the code embedded in the track as they walk along it. These functions can be seamlessly connected to computation circuits, which use molecular reaction networks that are composed of DNA and/or RNA and their modifying enzymes, such as DNA polymerases and exonucleases (Baccouche et al., 2014). These circuits include well-designed networks that undergo synthesis and degradation of DNA fragments, forming positive and negative feedback loops.

Furthermore, using nucleic acids as both an interface and the infrastructure of the system, it would be possible to build a complex hierarchical system by connecting the various synthetic modules that have been developed to date. This strategy might enable us to build synthetic ‘cells’ using the power of self-organization. The cells would, of course, look different from natural living cells, but they would have the basic functionality of cells to sense their environment, harvest energy and perform computation, as well as affect their surroundings. Although recreating the ‘magic’ of self-organization is non-trivial, this is a truly synthetic approach to biology that, ultimately, could lead to a deeper understanding of life.

Last of all, I believe that research into molecular motors is now at a stage similar to when Michael Faraday developed the electric motor 200 years ago. At that time, few people understood the potential uses of these newly developed electric motors, but now they are so widespread that it is difficult to find any machine that does not contain one. In the near future, more efficient and easy-to-manufacture biomimetic molecular motors and other nanomachines will appear, and they might, similarly, become indispensable elements in human society. One of the major challenges will be to design and control the motion of individual motor molecules and their hierarchical self-organization. Recently developed approaches, such as artificial intelligence-assisted design and evolutionary engineering, could be key to realizing such nanomachine-based systems in the next few decades.

Funding

This work was supported by Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) KAKENHI grants JP18H05420 and JP18H02417 to K.F.

Baccouche
,
A.
,
Montagne
,
K.
,
Padirac
,
A.
,
Fujii
,
T.
and
Rondelez
,
Y.
(
2014
).
Dynamic DNA-toolbox reaction circuits: a walkthrough
.
Methods
67
,
234
-
249
.
Ibusuki
,
R.
,
Morishita
,
T.
,
Furuta
,
A.
,
Nakayama
,
S.
,
Yoshio
,
M.
,
Kojima
,
H.
,
Oiwa
,
K.
and
Furuta
,
K.
(
2022
).
Programmable molecular transport achieved by engineering protein motors to move on DNA nanotubes
.
Science
375
,
1159
-
1164
.
Nicolau
,
D. V.
, Jr
,
Lard
,
M.
,
Korten
,
T.
,
Van Delft
,
F. C.
,
Persson
,
M.
,
Bengtsson
,
E.
,
Mansson
,
A.
,
Diez
,
S.
,
Linke
,
H.
and
Nicolau
,
D. V.
(
2016
).
Parallel computation with molecular-motor-propelled agents in nanofabricated networks
.
Proc. Natl. Acad. Sci. U S A
113
,
2591
-
2596
.
Nitta
,
T.
,
Wang
,
Y.
,
Du
,
Z.
,
Morishima
,
K.
and
Hiratsuka
,
Y.
(
2021
).
A printable active network actuator built from an engineered biomolecular motor
.
Nat. Mater.
20
,
1149
-
1155
.
Rothemund
,
P. W.
(
2006
).
Folding DNA to create nanoscale shapes and patterns
.
Nature
440
,
297
-
302
.
Seeman
,
N. C.
(
2010
).
Nanomaterials based on DNA
.
Annu. Rev. Biochem.
79
,
65
-
87
.
van den Heuvel
,
M. G.
and
Dekker
,
C.
(
2007
).
Motor proteins at work for nanotechnology
.
Science
317
,
333
-
336
.

Competing interests

The authors declare no competing or financial interests.