New paper on how active fluid framework explain vertical growth of biofilm

We have a new paper on Physical Biology titled, “Biofilm vertical growth dynamics are captured by an active fluid framework”. It was first authored by Dr. Raymond Copeland.

In this study, we showed that biofilm vertical growth dynamics can be rigorously described using an active fluid framework. Our model demonstrated that death–decay and reaction diffusion dynamics are central determinants of biofilm height, unifying empirical heuristic models with biophysical theory. This work provides a predictive framework for microbial architecture and highlights new physical levers for controlling biofilm development.

New paper on how friction controls biofilm development

We have a new paper on bioRxiv on how friction influences the development of bacterial biofilm. It was co-first-authored by Dr. Aawaz R. Pokhrel and Dr. Raymond Copeland.

In this work, we demonstrated that cell–substrate friction is a key physical parameter controlling biofilm morphology and expansion. Using white-light interferometry, we quantified how increasing surface friction increases biofilm contact angles and slows horizontal growth, consistent with a dynamic force balance model. These results establish friction as a general and overlooked determinant of biofilm development across diverse bacterial species.

Congratulations, Dr. Raymond Copeland!

Raymond Copeland defended and received his PhD in quantitative biosciences April 25th this year titled “Physical Simulations of Microbial Communities Under Stress” where he investigated how microbes grow, compete, and evolve resistance in complex communities using a combination of computational modeling, mathematics, and imaging. Ray joined the Yunker lab in early 2020 while he was still an undergraduate at Georgia Tech and stayed for graduate school to continue work with Dr Yunker and his friends. He enjoys classical music, chess, video games, and his wife Zoe. Ray remains at Georgia Tech to work as a postdoc with Dr Yunker

New paper on how snowflake yeast overcome biophysical limits to large size

We have a new paper in Science Advances on how snowflake yeast overcome diffusion limits via metabolically-driven flow. It was co-first-authored by Emma Bingham, in collaboration with the Thutupalli lab at NCBS and the Ratcliff lab at Georgia Tech.

metabolically driven flow img

The ecological and evolutionary success of multicellular lineages stems substantially from their increased size relative to unicellular ancestors. However, large size poses biophysical challenges, especially regarding nutrient transport: These constraints are typically overcome through multicellular innovations. Here, we show that an emergent biophysical mechanism—spontaneous fluid flows arising from metabolically generated density gradients—can alleviate constraints on nutrient transport, enabling exponential growth in nascent multicellular clusters of yeast lacking any multicellular adaptations for nutrient transport or fluid flow. Beyond a threshold size, the metabolic activity of experimentally evolved snowflake yeast clusters drives large-scale fluid flows that transport nutrients throughout the cluster at speeds comparable to those generated by ciliary actuation in extant multicellular organisms. These flows support exponential growth at macroscopic sizes that theory predicts should be diffusion limited. This demonstrates how simple physical mechanisms can act as a “biophysical scaffold” to support the evolution of multicellularity by opening up phenotypic possibilities before genetically encoded innovations.

New Publication on Morphological Entanglement in Living Systems

We have a new paper in Physical Review X on Morphological Entanglement in Living Systems, first-authored by Dr. Thomas Day and in collaboration with friends in the Ratcliff Lab at Georgia Tech.

Many organisms exhibit branching morphologies that twist around each other and become entangled. Entanglement occurs when different objects interlock with each other, creating complex and often irreversible configurations. This physical phenomenon is well studied in nonliving materials, such as granular matter, polymers, and wires, where it has been shown that entanglement is highly sensitive to the geometry of the component parts.

However, entanglement is not yet well understood in living systems, despite its presence in many organisms. In fact, recent work has shown that entanglement can evolve rapidly and play a crucial role in the evolution of tough, macroscopic multicellular groups. Here, through a combination of experiments, simulations, and numerical analyses, we show that growth generically facilitates entanglement for a broad range of geometries. We find that experimentally grown entangled branches can be difficult or even impossible to disassemble through translation and rotation of rigid components, suggesting that there are many configurations of branches that growth can access that agitation cannot. We use simulations to show that branching trees readily grow into entangled configurations. In contrast to nongrowing entangled materials, these trees entangle for a broad range of branch geometries. We, thus, propose that entanglement via growth is largely insensitive to the geometry of branched trees but, instead, depends sensitively on timescales, ultimately achieving an entangled state once sufficient growth has occurred. We test this hypothesis in experiments with snowflake yeast, a model system of undifferentiated, branched multicellularity, showing that lengthening the time of growth leads to entanglement and that entanglement via growth can occur for a wide range of geometries. Taken together, our work demonstrates that entanglement is more readily achieved in living systems than in their nonliving counterparts, providing a widely accessible and powerful mechanism for the evolution of novel biological material properties.

Farewell to Dr. Thomas Day

The most recently graduated member of the Yunker Lab, Thomas studied how physics constrains the evolution of early multicellular organisms. He defended his thesis in February 2023. It was titled Biophysical Constraints of Multicellularity: Building a Darwinian Material.

“Speedy” Tom Day grew up in the small town of Haddam, Connecticut, and ran Cross Country and Track & Field at Lafayette College while pursuing his undergraduate degree. At Georgia Tech, he kindled a new love for long bike rides. Among other activities, he also enjoys playing and listening to live music; this has led to an emergence of an N+1 problem, regarding how many instruments he owns vs. how many he needs.

Tom left Georgia Tech to start a postdoc with Julia Schwartzman at USC. He was a core part of our lab’s social and scientific lives, and we will miss him greatly. We are excited to see what Tom will do in the future!

New article on the vertical growth of biofilms

We have a new paper on the vertical growth of biofilms.

The primary mode for microbial life on Earth is the biofilm, in which microbes attach to a surface and then reproduce, forming crowded, growing communities. As these colonies develop, they expand horizontally and vertically. While horizontal growth across the surface is well studied, much less is known about the vertical growth of biofilms. This knowledge gap persists despite the importance of vertical growth for determining access to nutrients and oxygen—as well as the fact that vertical growth dynamics represent a fundamental aspect of biofilm physiology.

The lack of clarity about vertical growth dynamics is due in part to the experimental difficulty in measuring the height of a biofilm with sufficient precision over many different time scales in a non-destructive manner. Common techniques for characterizing the height and topographies of colonies lack the requisite resolution (e.g., confocal microscopy), are too slow and potentially destructive (e.g., atomic force microscopy), or do not allow time lapse measurements (e.g., scanning electron microscopy). Thus, we lack an empirical picture of how vertical growth dynamics proceed over short and long time scales. We overcome these barriers using white-light interferometry, which enables us to continuously measure the topography of developing biofilms with nanometer resolution out-of-plane. With this technique, we measured the topographies of a diverse cohort of microbes, including: prokaryotes and eukaryotes, gram positive and gram negative bacteria, anaerobic and aerobic species, different cell sizes and shapes, and differences in extracellular matrix production. Thanks to their unprecedented high spatial and temporal resolution, these measurements enabled us to determine how, exactly, vertical growth proceeds.

New paper on maximum entropy cell packing

We have a new paper from grad student Tom Day, and in collaboration with Prof. Will Ratcliff (GT) and Prof. Ray Goldstein (Cambridge).

The success of multicellular organisms is due in part to their ability to assemble cells into complex, functional arrangements. However, self-assembly is subject to random noise that affects the final emergent structure. As the physiology of multicellular organisms can depend sensitively on structural details—in particular, the geometry of cellular packing—these fluctuations can directly impact fitness. Further, while extant multicellular organisms possess developmental mechanisms that can suppress or make use of random noise, nascent multicellular organisms do not possess such developmental programs, yet must generate repeatable multicellular structures to be successful. Understanding the origin and evolution of multicellularity thus requires understanding the impact of random noise on multicellular self-assembly.

Addressing this topic is particularly challenging as multicellularity has evolved independently over 25 times, and each separate lineage has evolved different rules for assembly. There are thus few, if any, general principles uniting multicellular organisms with different growth morphologies. For example, organisms that grow with persistent mother-daughter bonds (like plants or fungi) `freeze’ structural randomness in place; in contrast, organisms with ‘sticky’ cell-cell adhesion (like animals) can rearrange, so their final structure will be impacted by noise in reproduction and intercellular interactions. But this comparison only scratches the surface of the diversity of multicellular structures (e.g., from biofilms to trees to whales), which vary in dimensionality, topology, evolutionary history, and more. It thus would appear that random noise manifests uniquely in different kinds of multicellular organisms, without uniting rules.

In this paper, we show that random fluctuations in cell packing geometry follow a universal distribution, predictable from the maximum entropy principle. We experimentally observe this distribution in both snowflake yeast, a lab-created multicellular organism and the green alga Volvox carteri, which first evolved multicellularity in the Triassic. Maximum entropy cell packing statistics therefore unite organisms with and without canalized multicellular development, and organisms with markedly different growth morphologies. With these experimental observations and additional computational simulations, we show that maximum entropy packing is a fundamental property of multicellular groups, independent of growth morphology. 

Using snowflake yeast, we also show that maximum entropy cell packing plays a central role in the transition to multicellularity. The multicellular life cycle in this model system (growth of the group followed by fracture into multiple groups) arises directly from the maximum entropy distribution of free space within multicellular clusters. In fact, we show that the distribution of size across the population is completely predictable from maximum entropy considerations. Variation in the statistics of cellular packing therefore underlies the emergence of repeatable multicellular traits, such as group size at fracture, demonstrating how randomness can underlie the emergence of heritable multicellular traits prior to the evolution of multicellular development.

In a related vein, a theoretical analysis of V. carteri shows that the effects of fluctuations in intercellular space on the motility of green algae is small. These results show that the effects of random cell packing can be beneficial, detrimental, or neutral in character.

In summary, we show that the maximum entropy principle guides the organization of cellular space in organisms that are profoundly different: varying in their developmental regulation, and generating multicellular structures with different growth morphologies and dimensionalities. These fluctuations in multicellular packing appear as unavoidable as thermal fluctuations are to equilibrium phenomena, suggesting that maximum entropy packing statistics may represent a general principle, uniting all multicellular organisms.