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A photosynthetic engine for artificial cells

Researchers engineer a cell-like structure that harnesses photosynthesis to perform designer reactions

By Leah Burrows, SEAS Communications

(CAMBRIDGE, Mass.) — In the quest to build an artificial cell, there are two approaches: the first reengineers the genomic software of a living cell, while the second focuses on cellular hardware by building simple, cell-like structures from the ground up that mimic the function of living cells. One of the biggest challenges in this second approach is mimicking the intricate chemical and biological reactions required for cells to perform complex behaviors.

A photosynthetic engine for artificial cells
A membrane (red outer boundary) encapsulates actin fibers (white lines), the protein building blocks of the cytoskeleton and tissues. The actin was polymerized by coupling ATP synthesis with artificial organelles (green dots) inside the membrane. Credit: Disease Biophysics Group/Harvard University

Now, an international team of researchers from the Wyss Institute at Harvard University, Harvard’s School of Engineering and Applied Sciences (SEAS), and Sogang University in Seoul have engineered a cell-like structure that harnesses photosynthesis to perform metabolic reactions, including energy harvesting, carbon fixation and cytoskeleton formation.

The research is published in Nature Biotechnology.

“This research, part of a rich collaboration between Harvard and Sogang University, opens up several different fronts on what could be done at the cellular level,” said Kit Parker, Ph.D., a Founding Core Faculty member of the Wyss Institute who is also the Tarr Family Professor of Bioengineering and Applied Physics at SEAS and co-principal investigator of the project. “We have activated metabolic activity with light, built an on-demand protein network in a living cell, and packaged all of the components required to do this into one cell.”

“The mechanisms we have demonstrated should be the first step in the development of multiple regulatory networks for artificial cells that can exhibit homeostasis and complex cellular behaviors,” said Kwanwoo Shin, Ph.D., Director of the Institute of Biological Interfaces and Professor in the Chemistry Department at Sogang University, and co-principal investigator of the project.

To build this synthetic system, the researchers engineered a photosynthetic organelle from the unique components of the plant and animal world.

“Our idea was simple,” said Keel Yong Lee, Ph.D., a postdoctoral fellow at SEAS and first author of the research. “We chose two protein photoconverters — one from plants, the other from bacteria — which can generate a gradient across the cellular membrane to trigger reactions.”

The photoconverters are sensitive to different wavelengths of light: one red, the other green. The proteins were embedded in a simple lipid membrane, along with enzymes that generate adenosine triphosphate (ATP), the essential energy carrier of cells. When the membrane is illuminated with red light, a photosynthetic chemical reaction occurs, producing ATP. When the membrane is illuminated with green light, the production stops. The ability to turn energy production on and off allows the researchers to control many reactions within the cell, including the polymerization of actin, the quintessential building block of cells and tissues.

A photosynthetic engine for artificial cells
The photosynthetic protein in the lipid membrane of the artificial cell generates a chemical reaction which produces actin filaments. Credit: Disease Biophysics Group/Harvard University

“Previous research in the field used these proteins to generate ATP, but only ever one at a time,” said Sung-Jin Park, Ph.D., a research associate at the Wyss Institute and SEAS and co-author of the paper. “We have combined the best of the plant world with the best of the animal world, allowing us to tune and regulate the energy production of the cell. We are engineering these cells from the bottom up, starting with these individual proteins.”

Being able to control and tune the production of actin allows researchers to control the shape of cell membranes and may provide a way to engineer mobile cells. This bottom-up approach could be used to build other artificial organelles, such as the endoplasmic reticulum or a nucleus-like system, and could be the first step towards artificial cell-like systems that can mimic the complex behaviors of biological cells.

“Introducing networks of functional proteins and organelles into an artificial cellular environment will pave the way to achieving the great goal of building a cell de novo,” said Shin.

“From fertility medicine to trauma wounds, and on to other, more exotic diseases, we now have a basic understanding of the tools and requirements to control what happens in a cell. The idea of cellular prosthetics is getting closer and closer with this result.” said Parker.

The research was co-authored by Keon Ah Lee, Ph.D., a Postdoctoral Researcher at Sogang University; Se-Hwan Kim, a researcher at Sogang University; Heeyeon Kim, a researcher at Sogang University; Yasmine Meroz, Ph.D., a Postdoctoral Researcher at SEAS; L. Mahadevan, Ph.D., a former Core Faculty member of the Wyss institute and the Lola England de Valpine Professor of Applied Mathematics at SEAS; Kwang-Hwan Jung, Ph.D., Professor and director of the Protein Biochemistry Laboratory at Sogang University, and Tae Kyu Ahn, Ph.D., Principal Investigator of the Department of Energy Science at Sungkyunkwan University.

This work was supported by the Mid-Career Researcher Program, Foreign Research Institute Recruitment Program, ARCNEX, the NRF of the Korea and National Research Council of Science and Technology (NST) through the Degree and Research Center (DRC) Program, and the Woo Jang Chun Special Project of the Rural Development Administration, Korea.

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