Using Light to Control the Forces Generated by Cells Inside Tissues

Optogenetics can help manipulate patterns of force within cells in fruit fly embryos

Aug 16 2021 | Credit: Marisol Herrera-Perez, Kasza Living Materials Lab, Columbia Engineering
activate or deactivate myosin activity

Optogenetic control of the force-generating myosin II motor protein (magenta) inside cells (green) during tissue development. Changes in myosin activity in the image at right are rapidly induced by blue light. Compare to image at left of a normal tissue.

New York, NY—August 16, 2021— During embryonic development, tissues and organs are sculpted by shifting patterns of forces produced by cells whose origins and effects mostly remain a mystery. Now researchers at Columbia Engineering have developed a new technique to manipulate these patterns using light to help scientists learn more about how these forces impact cells and tissues during the earliest stages of life.

Dramatic changes in shape during embryonic development are largely the result of contractile forces generated by networks of proteins within cells, which consist of actin filaments and myosin motor proteins. "In order to generate a specific tissue shape, the forces generated by cells are arranged in specific patterns, allowing a tissue to bend, fold, or stretch," said study first author Marisol Herrera-Perez, a postdoctoral research associate in the lab of Karen E. Kasza, the Clare Boothe Luce Assistant Professor of Mechanical Engineering at Columbia University. "However, we don't know much about how these patterns of forces are generated and then translated into tissue-level shape changes."

Now Kasza, Herrera-Perez, and their colleagues have developed a way to precisely tinker with these forces using optogenetics, a technique in which researchers modify the DNA of cells so bursts of light can activate or suppress specific proteins. Their study appeared online July 20 in Biophysical Journal.

"For centuries, scientists and engineers have observed the amazing changes in tissue shape and structure that occur during the embryonic development of animals. However, to really understand how these complex mechanical events work, we need tools to manipulate the mechanical forces driving these changes inside cells and tissues. This has been nearly impossible up to now," Kasza said. "Emerging optogenetic tools to manipulate mechanical forces, developed by our lab and others, have the potential to greatly accelerate our ability to understand these complex and crucial events in development."

The researchers incorporated light-sensitive proteins isolated from plants into the genome of the fruit fly Drosophila melanogaster. "These proteins respond to blue light, and so by shining blue light on the cell or tissue of interest at very specific times during development, we can turn on the tools to manipulate forces with high spatial and temporal specificity," Herrera-Perez said.

Optogenetic control of the force-generating myosin II motor protein (magenta) inside cells (green) during tissue development. Changes in myosin activity in the video at right are rapidly triggered by blue light. Compare to video at left of a normal tissue.

The scientists were able to use light to rapidly activate or deactivate myosin activity with enough strength to override existing patterns of mechanical forces in cells, altering cell movements and shapes.

"The fact that we can override an existing force pattern is important, because the set of instructions or steps that an embryo follows during development is very robust, and to perturb them, we usually need methods like genetic mutations or drug injections," Herrera-Perez said. "Achieving such perturbations using optogenetics and light opens up a pathway to flexibly target cellular forces at the precise location and time point we want during development."

Specifically, the researchers studied the process of axis elongation in the fruit fly, where a tissue narrows in one direction and extends along the other direction to rapidly elongate the head-to-tail axis of the embryo. "A similar process occurs in humans as well," Herrera-Perez said. "We showed that modifying the mechanical forces in the tissue affects the way cells behave, for example, how they change shape and how they pack themselves into the tissue. This is helping us to understand how the tissue changes shape and elongates so rapidly and efficiently during normal development."

"The next step is to use these optogenetic tools both to explore how mechanical forces help regulate tissue development in the embryo and to control the mechanics and shape of tissues cultured in the laboratory for a wide range of applications in engineering, biology, and medicine," Kasza said.

Columbia Engineering

Columbia Engineering, based in New York City, is one of the top engineering schools in the U.S. and one of the oldest in the nation. Also known as The Fu Foundation School of Engineering and Applied Science, the School expands knowledge and advances technology through the pioneering research of its more than 220 faculty, while educating undergraduate and graduate students in a collaborative environment to become leaders informed by a firm foundation in engineering. The School’s faculty are at the center of the University’s cross-disciplinary research, contributing to the Data Science Institute, Earth Institute, Zuckerman Mind Brain Behavior Institute, Precision Medicine Initiative, and the Columbia Nano Initiative. Guided by its strategic vision, “Columbia Engineering for Humanity,” the School aims to translate ideas into innovations that foster a sustainable, healthy, secure, connected, and creative humanity.

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Holly Evarts, Director of Strategic Communications and Media Relations

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ABOUT THE STUDY

The study is titled "Using optogenetics to link myosin patterns to contractile cell behaviors during convergent extension."

The study appeared in Biophysical Journal on July 20, 2021.

Authors are: R. Marisol Herrera-Perez, Christian Cupo, Cole Allan, Annie Lin, and Karen E. Kasza.

Department of Mechanical Engineering, Columbia Engineering

This work was supported by NSF Civil, Mechanical, and Manufacturing Innovation Grant 1751841. Karen E. Kasza holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, a Clare Boothe Luce Professorship, and a Packard Fellowship.