Conference-ing in a Virtual World

This blog was written by Nancy Beam, Senior Editor, PLOS ONE

AIDS 2020: Virtual, the 23rd International AIDS Conference hosted by the International AIDS Society, may portend the future of international conferences regardless of when the COVID-19 pandemic is brought under control. AIDS 2020 was originally planned to take place in San Francisco and Oakland, California from July 6-10. This two-city format, itself a revolutionary innovation, was meant to highlight the health disparities and innovative responses to HIV/AIDS of these two iconic cities. The organizers then switched to a completely virtual format in late March in response to the COVID-19 pandemic.

The virtual conference provided many advantages. The conference registration fees were greatly reduced. Travel, lodging, and poster-printing costs were eliminated. Travel hassles and jetlag did not decrease attendees’ ability to focus. Although the International AIDS Conference has always provided a platform for people living with HIV, community organizers, providers, and researchers to contribute, this conference seemed particularly suited to weaving different perspectives together. For example, Prime Sessions combined presentations by scientific experts on a topic with talks by community advocates about their work and lived experiences. Up-to-date findings were easily integrated into the conference program, and a free COVID-19 conference was added to the AIDS 2020 conference only two months before it was scheduled to begin.

Conversely, I missed the excitement of travel, meeting new people, and the atmosphere of exhilaration created by being in the same room with a large group of people. I missed running into old colleagues from the HIV/AIDS community and serendipitous conversations struck up while waiting in line or for presentations to start, or while gathered around a poster. While there were public chat forums meant to encourage these types of conversations, I didn’t find any substantive conversations going on there. Finally, I opted out of browsing through the exhibitions. Without the smell of fresh popcorn, the lure of free lattes, and the possibility of stocking up on the ubiquitous free pens, so beloved at last year’s conference, I didn’t wander through the exhibit booths on my way to somewhere else. I saw pop-up invites to talks and gatherings at booths, so I may have missed out on some engagement opportunities. Even at a virtual conference, there is still too much to do

Predictably, technical problems occurred and while travel barriers were eased, internet access remained a barrier for some participants especially for those who could not access their offices. In addition, because they weren’t traveling, some attendees reported that they were expected to continue working, making it difficult to attend sessions. While conference sessions will be available online for a month after the conference, the expectation that participants continue adding webinar viewing to their workday is a heavy burden. My expectation was that virtual attendance would increase the diversity of attendance as travel and cost barriers were decreased, but without seeing the data, I am not able to judge whether this occurred, or if work and internet access presented too great a barrier. I look forward to hearing what IAS reports about the impact on diversity.

I personally found the tech support to be quick and helpful. However, some website features were surprisingly unsophisticated. For example, the search function only allowed searching for one keyword at a time. So, searching for posters with the keyword “transgender” was quite specific, but “drug delivery systems” produced far too many false positives. Also, searches couldn’t be saved, so after viewing one poster or presentation on a topic, the search had to be rerun. I would have also liked to have been able to click on links in the conference program to go directly to sessions rather than having to navigate to sessions through a separate listings.

As with working remotely, having learned from this forced experiment the pros and cons of a virtual conference, the conferences of the future are likely to be different, and better, than before. A blend or virtual and in-person participation will make for a richer, more diverse, more accessible experience for all.

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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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