Physical forces at the interface with biology and chemistry: a conversation with Kerstin Blank and Matthew Harrington

 

Cell behaviour, tissue formation/regulation, physiology and disease are all influenced by cellular mechanics and physical forces. The field of mechanobiology has for a long time striven to fully understand how these forces affect biological and cellular processes, as well as developing new analytical techniques. At the same time, the properties of advanced smart materials, such as self-healing, self-reporting and responsive polymers, have been determined by a complex interplay between the thermodynamics, kinetics and mechanics of dynamic bonding strategies. These are tightly connected to the field of mechanochemistry, which aims to elucidate and harness molecular level design principles and translate these to the bulk material level as emergent properties. At this interface between disciplines lies an emerging and exciting research area that has been strongly facilitated by the collaboration of physicists, chemists, engineers, materials scientists, and biologists.

We had the pleasure of speaking to Kerstin Blank and Matthew Harrington, who have been working on how mechanical forces influence biological systems, molecules and responsive biomaterials, about their views of the field and the recent ‘Multiscale Mechanochemistry and Mechanobiology’ conference of which PLOS ONE was one of the proud sponsors.

 

How did you first become interested in this topic?

 

Kerstin: When I started in this field in 2000, I was mostly impressed by the technical possibilities. I was working with Hermann Gaub, one of the leaders in single-molecule force spectroscopy. I found it fascinating that we could stretch a single biological molecule and observe its response. I did ask myself sometimes if this was just something that physicists like to play with or if one could solve biomedically relevant questions with this approach. Now, almost 20 years later, it has become very evident that a large number of biological systems are regulated by mechanical forces in many different ways.

 

Matt: My educational background was primarily in biology and biochemistry, but I became fascinated with the capacity of certain biological materials to exhibit self-healing responses in the absence of living cells. I reasoned that this must arise from specific chemical and physical design principles in the material building blocks themselves, and I became obsessed with figuring out how this works. This led me to the self-healing materials community, which was largely populated with chemists and materials engineers, but not so many biologists. When I began to see that many of the same principles at play in synthetic self-healing materials were present in nature, and that in some cases nature was going well beyond the state of the art in synthetic self-healing materials, I realized the enormous potential at the interface of mechanobiology and mechanochemistry. I haven’t looked back since.

 

Which areas are you most excited about?

 

Kerstin: I find it very intriguing how cells utilize mechanical information from their environment and then feed it into intracellular biochemical signalling cascades. Understanding these mechanosensing and mechanotransduction processes requires knowledge of the cellular players and their interactions. But to develop the complete picture, we also need to investigate how cells interact with their extracellular environment. This also involves understanding the microscopic and macroscopic mechanical properties of the extracellular environment. I am highly excited about the development of molecular force sensors that convert mechanical force into a fluorescent signal. This allows for the localized detection of cell traction forces and, in the future, will also enable us to visualize force propagation inside materials that mimic the natural extracellular matrix.

 

Matt: I am currently most excited about understanding how and why nature uses different transient interactions to control the fabrication and viscoelastic mechanical responses of biopolymeric materials and the potential this has for the development of sustainable advanced polymers of the future. Recent discoveries in the field clearly show that in contrast to traditional polymers, living organisms commonly use specific supramolecular interactions based on dynamic bonds (e.g. hydrogen bonding, metal coordination or pi-cation interactions) to guide the self-assembly and mechanical properties of protein-based materials. The thermodynamic and kinetic properties of these labile bonds enable a certain dynamicity and responsiveness in these building blocks that provides potential inspiration for environmentally friendly materials processing and active/tuneable material properties. These concepts are already being adapted in a number of exciting bio-inspired polymers.

 

What progress has the field made in the last years?

 

Kerstin: It is now well-established that cells are able to sense and respond to the elastic and viscoelastic properties of the material they grow in. We have also learned a lot about how the mechanical signal is converted into biochemical signalling on the intracellular side. This is a direct result of many new technological developments, including the molecular force sensors described above. It is further a result of the increasing development of extracellular matrix mimics with well-defined and tuneable mechanical properties and microstructures.

 

Matt: Due to recent technological advances it is becoming possible to link specific aspects of mechanical material responses directly to structural features at multiple length scales. The better we understand these structure-property relationships, the better we can optimize the material response. This provides an intimate feedback loop that has enabled major breakthroughs in the fields of active matter, including self-healing and self-reporting polymers.

 

What is the real-world impact?

 

Kerstin: It is widely accepted that mechanical information plays a key role in stem cell differentiation. It has further been shown that mutated cells, e.g. in cancer or cardiovascular diseases, have different mechanical properties and show alterations in processing mechanical information. Understanding the origin of these changes and being able to interfere with them will have direct impact in disease diagnostics and treatment. Engineering materials with molecularly controlled structures and mechanical properties will further enable the community to direct stem cell differentiation in a more defined manner for applications in tissue engineering and regenerative medicine.

 

Matt: Aside from biomedical impacts, the insights gained from understanding the structure-function relationships defining the mechanical response of molecules are also extremely relevant for the development and sustainable fabrication of next generation advanced polymers. Given the global threat of petroleum-based plastics processing and disposal, this is an extremely important aspect of the research in this field.

 

What are the challenges and future developments of the field?

 

Kerstin: At this moment, we usually try to relate the macroscopic material properties (measured in the lab) with the microscopic environment that cells sense. In my view, we are missing a key piece of information. We need to understand how the macroscopic properties of a material emerge from its molecular composition, topography and hierarchical structure. In combination, all these parameters determine the mechanical properties of a material and, more importantly, what the cells ‘see’. In fact, this is not only key for the development of new extracellular matrix mimics. The same questions need to be answered for understanding how nature assembles a wide range of structural and functional materials with outstanding properties, such as spider silk, cellulose composites and nacre. Here, I see a great potential for future collaboration between disciplines.

 

Matt: There are enormous challenges on the bio-inspiration side of the field involved with transferring design principles extracted from biological materials into synthetic systems. Biology is inherently complex, so there is a common tendency to distil the extracted concept to a single functional group or concept, while often there are collective effects that are lost by this more reductionist approach. On the biological side, a key challenge is ascertaining which are the relevant design principles. On the bio-inspired side, there are challenges in finding appropriate synthetic analogues to mimic the chemical and structural complexity of the natural system. Overcoming this barrier requires cross-disciplinary communication and feedback and is an extremely exciting and active area in our field.

 

Why and when did you decide to organize a conference on this topic?

 

Kerstin & Matt: While both working at the Max Planck Institute of Colloids and Interfaces, we quickly realized that the cell biophysics, biomaterials, mechanochemistry and soft matter communities are all interested in very similar questions while using similar methods and theoretical models; however, we had the impression that they hardly interact with each other. We thought of ways to change this and organizing a conference was clearly one way to do it. The first conference with the topic ‘Multiscale Mechanochemistry and Mechanobiology: from molecular mechanisms to smart materials’ took place in Berlin in 2017. When bringing this idea forward in our respective communities, we immediately realized that we hit a nerve. Now that the conference has taken place for the second time in Montreal in 2019, we really got the feeling that we are starting to create a community around this topic. There will be another follow up conference from August 23-25, 2021 in Berlin (@mcb2021Berlin).

 

What are the most interesting and representative papers published in PLOS ONE in this field?

 

Kerstin: The paper ‘Monodisperse measurement of the biotin-streptavidin interaction strength in a well-defined pulling geometry’, published by Sedlak et al., is a highly interesting contribution to the field of single-molecule force spectroscopy, which was also presented at the conference. This work highlights the methodological developments in single-molecule force spectroscopy since its very early days. The authors from the Gaub lab have re-measured the well-known streptavidin-biotin interaction, now with a very high level of control over the molecular setup. It clearly shows how far the field has come and also that protein engineering, bioconjugation chemistry, instrumentation development and data analysis all need to go hand in hand to obtain clear and unambiguous experimental results. Clearly, considering a defined molecular setup is not only crucial for this kind of measurement but also for the development of biomimetic materials with controlled mechanical properties.

 

Sedlak SM, Bauer MS, Kluger C, Schendel LC, Milles LF, Pippig DA, et al. (2017) Monodisperse measurement of the biotin-streptavidin interaction strength in a well-defined pulling geometry. PLoS ONE 12(12): e0188722, https://doi.org/10.1371/journal.pone.0188722 

 

Matt: Accurately detecting and measuring the mechanical forces at play inside living cells is one of the key challenges in the field of mechanobiology, given the small size and dynamic nature of the intracellular environment. However, this information is extremely important for understanding the role of mechanics in regulating cellular functions such as growth, differentiation and proliferation, as well as disease states. In the ‘Nuclei deformation reveals pressure distributions in 3D cell clusters’ paper from the Ehrlicher group, the authors address this challenge by using fluorescently labelled proteins in the cell nucleus coupled with confocal microscopy to measure compressive pressures within cells and cell clusters. Using this methodology, they explored the effect of cell number and shape of multicellular clusters on the internal compressive pressure within cells, providing potentially important insights for cellular signalling and function. These studies have potential applications in both in vitro and in vivo models, and provide a relatively simple methodology for acquiring intracellular mechanical data.

 

Khavari A, Ehrlicher AJ (2019) Nuclei deformation reveals pressure distributions in 3D cell clusters. PLoS ONE 14(9): e0221753, https://doi.org/10.1371/journal.pone.0221753

 

 Other PLOS ONE representative papers:

 

  • Huth S, Sindt S, Selhuber-Unkel C (2019) Automated analysis of soft hydrogel microindentation: Impact of various indentation parameters on the measurement of Young’s modulus. PLoS ONE 14(8): e0220281, https://doi.org/10.1371/journal.pone.0220281
  • Taufalele PV, VanderBurgh JA, Muñoz A, Zanotelli MR, Reinhart-King CA (2019) Fiber alignment drives changes in architectural and mechanical features in collagen matrices. PLoS ONE 14(5): e0216537. https://doi.org/10.1371/journal.pone.0216537
  • Wheelwright M, Win Z, Mikkila JL, Amen KY, Alford PW, Metzger JM (2018) Investigation of human iPSC-derived cardiac myocyte functional maturation by single cell traction force microscopy. PLoS ONE 13(4): e0194909. https://doi.org/10.1371/journal.pone.0194909
  • Opell BD, Clouse ME, Andrews SF (2018) Elastic modulus and toughness of orb spider glycoprotein glue. PLoS ONE 13(5): e0196972. https://doi.org/10.1371/journal.pone.0196972
  • Yalak G, Shiu J-Y, Schoen I, Mitsi M, Vogel V (2019) Phosphorylated fibronectin enhances cell attachment and upregulates mechanical cell functions. PLoS ONE 14(7): e0218893. https://doi.org/10.1371/journal.pone.0218893

 

Kerstin Blank studied Biotechnology at the University of Applied Sciences in Jena and obtained her PhD in Biophysics under the supervision of Prof Hermann Gaub at Ludwig-Maximilians Universität in Munich. After two postdocs at the Université de Strasbourg and the Katholieke Universiteit Leuven, she became an Assistant Professor at Radboud University in Nijmegen in 2009. In 2014, she moved to the Max Planck Institute of Colloids and Interfaces where she holds the position of a Max Planck Research Group Leader. Her research interests combine biochemistry and single molecule biophysics with the goal of developing molecular force sensors for biological and materials science applications.

 

Matthew J. Harrington is Canada Research Chair in Green Chemistry and assistant professor in Chemistry at McGill University since 2017. He received his PhD in the lab of J. Herbert Waite from the University of California, Santa Barbara. Afterwards, he was a Humboldt postdoctoral fellow and then research group leader at the Max Planck Institute of Colloids and Interfaces in the Department of Biomaterials. His research interests are focused on understanding biochemical structure-function relationships and fabrication processes of biopolymeric materials and translating extracted design principles for production of sustainable, advanced materials.

 

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It’s the little things- An interview with the Guest Editors of our Microbial Ecology of Changing Environments Call for Papers

PLOS ONE has an open Call for Papers on the Microbial Ecology of Changing Environments, with selected submissions to be featured in an upcoming Collection. We aim to highlight a range of interdisciplinary articles showcasing

It’s the little things- An interview with the Guest Editors of our Microbial Ecology of Changing Environments Call for Papers

PLOS ONE has an open Call for Papers on the Microbial Ecology of Changing Environments, with selected submissions to be featured in an upcoming Collection. We aim to highlight a range of interdisciplinary articles showcasing the diversity of systems, scales, interactions and applications in this dynamic field of research.

We spoke to the Guest Editors for this project, Melissa Cregger and Stephanie Kivlin, about what motivates their research and the challenges and opportunities faced by microbial ecologists.

 

What makes microbes so interesting?

MC: Microorganisms are everywhere and are important members of all of the ecosystems they inhabit. There are microorganisms in soils, oceans, lakes, and even within our bodies. Within all of these habitats they are performing really important functions. In lakes, oceans, and soils, microorganisms are key to moving nutrients around. Within our bodies, they aid in things like digestion and disease prevention.

SK: Microorganisms are fascinating in how genetically diverse and numerous they are. Microorganisms can be found in almost every habitat on Earth and are often the first to respond to environmental disturbance and global change. Thus, microorganisms likely hold the key to solving most of Earth’s problems as we face global climate change.

 

How is microbial ecology relevant to major environmental and societal issues like climate change and food security?

MC: Given how ubiquitous microorganisms are across the world, understanding how they function is key if we want to understand and mitigate the consequences of climatic change and if we want to grow food more sustainably and in marginal lands. For instance, if we can get a better understanding of microbial carbon cycling, we can potentially use biological carbon capture as a mitigation strategy to help combat rising levels of atmospheric carbon dioxide. Additionally, researchers around the world are trying to understand how plants interact with microbial communities in an effort to harness these microbes to increase food production and the ability of plants to withstand changing abiotic conditions.

SK: Microorganisms are the key for innovating nature-based solutions to climate change. For example, specific fungal symbionts of plants can be tailored to increase agricultural plant drought tolerance. Other microorganisms may be deployed to remediate oil spills or other man-made pollutants. Finally, engineering plant-microbial associations may lead to a larger terrestrial carbon sink to offset atmospheric CO2 concentrations, creating a negative feedback to climate change itself.

 

Tell us a bit about your own research and how it ties in with some of these issues.

MC:  A large portion of my research is focused on understanding how to use beneficial microbes to increase plant productivity and tolerance to drought, and also in understanding how these communities function in the soil environment with the ultimate goal of using them to enhance ecosystem stability. I am part of two large multi-disciplinary teams at Oak Ridge National Laboratory that are specifically focused on plant-microbe interactions in the potential biofuel feedstock, Populus. We are trying to characterize basic principles governing plant-microbe interactions in the hope of making Populus a better biofuel that can grow in marginal lands with limited input of fertilizer and water.

SK: Research in the Kivlin Lab aims to create distribution models for terrestrial microorganisms and their functions. Our current focus is on arbuscular mycorrhizal (AM) fungi, as these plant symbionts are the main providers of nutrients and drought tolerance to agricultural plants. We are interested in where these fungi are, the ecosystem-level carbon and nutrient cycling they promote and how sensitive these plant-fungal interactions may be to climate change. To address these questions, we both compile data on AM fungal distributions worldwide, but also examine plant-AM fungal interactions along altitudinal gradients that serve as a space for time substitution for climate change and in long-term climate change experiments.

 

How are technological advances opening up new opportunities in your field?

MC: Over the last 20 years there have been rapid advances in sequencing and molecular techniques that have enabled amazing opportunities in microbial and ecosystem ecology. We are finally able to identify unculturable microorganisms inhabiting diverse communities using next generation sequencing and are getting clues into their function using metagenomics, metatranscriptomics, proteomics, and metabolomics. Further, using these techniques, people are developing some new strategies to culture more microbes.

SK: It is increasingly clear that the genomics revolution has impacted microbial ecology. We now can link functional genetic potential to microorganisms in environmental microbiomes and understand how interactions among microorganisms and between microorganisms and plants control expression of these functional genes and the metabolites they code for.

 

How does microbial ecology benefit from interdisciplinary collaboration?

MC: Microbial communities are incredibly complex, therefore understanding their role in ecosystems really requires a systems biology approach. Because of this, having an interdisciplinary team to tackle questions at various scales is really important.

SK: Microbial ecology is inherently interdisciplinary. We collaborate with earth system modelers to scale microbial function from the organism to the globe and with geneticists to understand the genetic underpinnings of those functions. Without these collaborations, our field would be siloed to case-studies of microbial communities and lack the ability to develop first-principles theory across microbial communities and environments.

 

What are some of the biggest unsolved questions in microbial ecology?

MC: There are so many unsolved questions in microbial ecology that it is hard to just identify a few. We still have a limited understanding of how microbial communities fluctuate through time. How stable are they within ecosystems? Are organisms within communities functionally redundant? Does this redundancy aid in resilience of the community post disturbance? How do these communities respond to fluctuations in abiotic variables? I could really go on and on.

SK: Despite all of the vital roles that microorganisms provide in the environment, we still don’t understand (1) where microorganisms even are spatially and what abiotic and biotic processes control these distributions, or (2) how temporally dynamic microbial communities are both within and among plant growing seasons. Answering these fundamental questions will allow us to understand linkages between microbial communities and plant growth, microbial composition and ecosystem carbon and nutrient cycles, and allow us to effectively manipulate microbial consortia for societal gain in agricultural and bioremediation settings.

 

The post It’s the little things- An interview with the Guest Editors of our Microbial Ecology of Changing Environments Call for Papers appeared first on EveryONE.

An Interview with Guest Editors for the Photovoltaic Materials Call for Papers

One of the most pressing challenges of the 21st century is meeting the ever-increasing demand for energy consumption whilst reducing the environmental impact of energy production and storage. Solar energy conversion devices have the potential

Tackling global biodiversity loss – An Interview with Biodiversity Conservation Call for Papers Guest Editor

  Human-induced environmental changes constitute the greatest current threat to biodiversity, comparable with other major extinction events observed in the Earth’s history. Biodiversity is the backbone of ecosystems and maintaining diversity through conservation is important