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Science
15 July 2024

How Do Cells Dance In Development?

A fascinating study explores phase transitions in biological tissues, revealing how cells switch between fluid-like and solid-like states to shape organs and structures during development.

Imagine the intricate ballet of a growing embryo, where cells sway and pivot as if guided by an unseen choreographer. This elegant dance is more than merely spectacular. It's a crucial process that shapes the tissues and structures of all living organisms. At the heart of this astonishing performance lies a fascinating concept: phase transitions in biological tissues.

A recent study published in Nature Communications delves into this captivating phenomenon, shedding light on how tissues transition from fluid-like to solid-like states during development. This not only expands our understanding of developmental biology but also opens avenues in tissue engineering and regenerative medicine. But what exactly are these phase transitions, and why do they matter?

Phase transitions might sound like something out of a physics lecture, where ice melts into water or water evaporates into steam. Surprisingly, similar principles apply to biological tissues. During development, tissues can shift between fluid and solid states, a process critical for their morphogenesis - the biological process that causes an organism to develop its shape.

Think of these transitions as a traffic system. In a high-density area, like a bustling city intersection, vehicles (or cells) move slowly and methodically, almost jammed. This is akin to a solid state where cells are tightly packed and movements are restricted. On the other hand, in a low-density countryside road, cars flow freely, similar to a fluid state in tissues where cells can move past each other with ease. This fluidity enables cells to migrate and reorganize, essential for forming complex structures during embryonic development.

A classic example of this fluid-to-solid transition can be observed in the early stages of vertebrate development, notably in zebrafish embryos. Here, cell density impacts local tissue stiffness, effectively controlling the transition from a fluid-like state, facilitating movement, to a more solid-like state, ensuring structural stability.

One might ask, how do researchers study these invisible phase transitions within the minuscule world of cells? The answer lies in a blend of innovative techniques borrowed from physics and material science. Mechanical properties of tissues can be assessed using rheological measurements, much like testing the firmness of a mattress by applying pressure and observing the resulting deformation. Methods like atomic force microscopy (AFM) and optical tweezers have been adapted to probe cellular-scale rheology.

For instance, AFM measures the elasticity of cells by using a tiny mechanical probe to press down on the cell surface and recording the resistance encountered. Optical tweezers, on the other hand, use the force of laser beams to move and manipulate cells, allowing scientists to measure their mechanical responses in real-time. A more recent addition is Brillouin microscopy, a label- and contact-free method that tracks shifts in tissue stiffness by observing how light waves scatter through the biological material.

Understanding these transitions isn't solely an academic exercise. The insights gleaned have profound implications. For one, they enhance our grasp of developmental disorders. Conditions like cancer often involve aberrant tissue mechanics, where cells either lose their regulated stiffness or fail to transition properly between states, leading to uncontrolled growth and metastasis.

Moreover, these principles can revolutionize tissue engineering. By mimicking the natural phase transitions of tissues, we can create better synthetic materials for medical applications. Consider bioprinting, where layer-by-layer a biological substance is printed to form tissues or organs. Controlled phase transitions can ensure these printed tissues exhibit the right mechanical properties, essential for functionality and integration into the body.

The study's findings emphasize that neither fluid nor solid states are permanent. Tissues dynamically modulate their properties through various internal and external cues. Internal mechanisms include cellular composition changes, such as adjustments in water content and cytoskeletal arrangements, while external factors often involve the extracellular matrix (ECM), a network of proteins and other molecules surrounding cells. The ECM can influence tissue stiffness and thus impact phase transitions.

These transitions are not always abrupt. Gradual changes in tissue stiffness can occur over several hours to days. For instance, plant cells adjust their rigidity through turgor pressure - the force exerted by water inside the cell against the cell wall. This pressure changes as water influx or efflux varies. In animals, similar modulations happen due to hormonal signals or changes in the mechanical environment.

As development progresses, cell division contributes to the regional modulation of tissue properties. During zebrafish gastrulation, a process where the embryo reorganizes itself to form different layers, central blastoderm cells round up during division, making the tissue more fluid-like. Conversely, marginal cells increase cohesion through signaling pathways, counteracting this effect to maintain overall structural integrity.

Equally fascinating is the interplay between cell density and tissue phase. High density can lead to a jamming effect, where cells become so packed they transition to a solid-like state. This is observed in various biological processes, from embryo development to tumor formation. For example, in confluent epithelial tissues, fluid-like behaviors arise from tightly packed cells' ability to rearrange and move collectively, while solid-like behaviors result from increased cell adhesion and reduced motility.

One compelling insight from the study is that these phase transitions and mechanical properties are not just passive responses. Cells actively contribute to these changes. Pulsed contractions of the actomyosin network, a structure of proteins within cells responsible for contraction and movement, can generate forces that influence tissue behavior. This dynamic modulation ensures tissues can adapt their mechanical state in response to developmental cues or environmental stressors.

While the study sheds significant light on the biological importance of phase transitions in tissues, it's not without limitations. Detecting these transitions with precision remains challenging due to the inherent complexity and variability of biological systems. Current techniques, though advanced, often provide indirect measurements requiring careful interpretation. Additionally, observational methods may not capture the full spectrum of dynamic changes occurring at the cellular and molecular levels.

Future research is poised to bridge these gaps. Combining mechanical characterization with advanced imaging and molecular biology techniques will offer deeper insights into the multiscale coupling of geometry, mechanics, and biochemistry in tissues. This holistic approach could unravel how collective cellular behaviors govern tissue formation and function and identify parameters controlling phase transitions during morphogenesis.

As we stand on the cusp of this exciting frontier, the implications for medicine, biology, and materials science are immense. Understanding how tissues transition between states provides a blueprint for engineering better biomaterials and developing treatments for diseases rooted in mechanical dysfunction. As the study eloquently concludes, future work should aim to elucidate the complex interplay of forces at play, shaping the collective behaviors of multicellular systems and steering the fascinating dance of life into new realms of discovery. "Going beyond phase transitions, future research should provide insight into the multiscale coupling of geometry, mechanics, and biochemistry and how they integrate to define the collective behaviors of multicellular systems".

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