Modeling and Quantifying Cell Function: 25 years of Cell Mechanobiology (16w5141)

Arriving in Banff, Alberta Sunday, October 9 and departing Friday October 14, 2016

Organizers

(University of Pennsylvania)

(University of Illinois at Urbana-Champaign)

(University of Toronto)

Objectives

Objective of the workshop: The primary objective and vision of the workshop are to (1) Reflect on the most critical and fundamental findings and concepts in quantitative cell mechanics to date, (2) Identify the challenges in the field, (3) Identify critical areas of its potential societal impact, e.g., health care, new paradigms in biohybrid devices, sensors and machines, and (4) propose potential roadmaps for the field to realize the potentials. The workshop will bring together 30-50 scientists in the field. There will be short lectures, Q&A sessions, panel discussions, and working group meetings. The invitees will include researchers with expertise in cellular biomechanics and biophysics, experimentalists and theorists, as well as a few clinicians who have experience and interest in applying quantitative concepts of novel analyses to biomedicine. The steering committee for the workshop consists of Taher Saif (UIUC), Paul Janmey (U Penn), and Craig Simmons (U-Toronto). The committee will meet frequently to select the invitees, finalize the format of the workshop, and work on a position paper that summarizes the outcome of the workshop.

Broader impact: The outcome of the workshop will be disseminated to the broader community, funding agencies, national labs and international institutes. The proposed future roadmap will have a significant impact on the graduate research and education curriculum in cell mechanics, and research directions for junior researches in the field.

The proposed workshop will be the first of its kind where the scientists will ask critical questions, such as: What is the impact of mathematical analyses of mechanobiology on biologists and the broader research community? Is there a tangible societal benefit in the near future? What are the critical questions in mechanobiology that need to be addressed by the community as a whole? Are there efforts that can be trimmed? What are the discrete paths to translation? The need for such a gathering and a list of topics

Until now, most labs in mechanobiology have directed their efforts in addressing focused questions, and often theorists as well as experimentalists have worked in relative isolation rather than together to identify the most promising areas of collaboration. Many of these questions were guided by the instrumentation, computational resources, and expertise accessible to and developed by the labs. In spite of collaborations between groups, the research efforts have remained highly focused. In addition, researchers contributing to mechanobiology are from diverse fields and geographically dispersed, and there are still barriers to communication due to specialized educational backgrounds and jargon. It is thus timely to explore the synergy between different areas of expertise, identify common tools and methods, and define grand challenges that need to be addressed by a coordinated effort of various labs.

Format of the workshop

The workshop will span 5 days, 8am-12 pm and 7 pm to 9 pm for the first four days, and 8-12:30 the fifth day. All participants will be in the same session for presentations, with ample time in the afternoon for discussions in smaller groups. The workshop will be organized as a set of themes. Within each theme, there will be subthemes or key words (e.g., statistical mechanics of soft cytoskeletal assembly, cell-ECM interactions, active matter, signal transduction, etc.) that will be suggested to the speakers to cover. Each speaker will have 20 to 40 mins to give a presentation. They will be requested to address 3 questions as part of their presentation: (1) In your opinion, what is the most important finding from your lab? (2) Identify a grand challenge in the field. (3) Identify an area where cell mechanobiology may have a long lasting impact.

Prior to the workshop, the attendees will be asked to propose broader questions (hopefully provocative) that they would like to be discussed during the workshop. They will also justify the importance and relevance of the question in the context of the state of the art. These questions will be posted on the workshop website. They will be reviewed by a group of graduate students who will rephrase the questions to reduce overlaps and redundancies, and to make them more readable and transparent to scientists from different backgrounds. The speakers can address some of these questions during their talks.

The fifth day of the workshop will have 4 panel sessions, each one hr long. Each panel will have two session chairs. They will summarize the discussions from the themes covered during the first four days, i.e., outline the grand challenges, potential impacts, and future roadmaps. The summary will be followed by discussions by the participants. The objective will be to clearly state the grand challenges and outline the future directions that transcend the thematic boundaries. Sample Themes to be covered:

Day 1

Relevant mechanical microenvironment in biology

Keywords: length, time and stiffness scales

Cell-matrix and cell-cell force interactions

Keywords: Force and stress scales, integrin and cadherin, focal complex

Intra-cellular forces

Keywords: motor proteins, actin-microtubule interactions, force induced protein conformations

Mechanisms of cell mechanotransduction

Keywords: transmembrane proteins, ion channels, transcription regulation

Day 2

Computational approaches to cell structure

Keywords: statistical mechanics of biopolymers; glassy dynamics; self assembly

Active systems

Keywords: motor proteins; non-equilibrium systems; fluctuation dissipation

Systems approach to mechanobiology

Keywords: emergent systems; feedback loops; genetic networks

Analyzing motility

Keywords: random walks; chemical and mechanics gradients; flocking

Day 3

Dynamic reciprocity between cells and microenvironment

Keywords: cellular sensing of stiffness, growth factors

Nuclear mechanotransduction

Keywords: chromatin rearrangement, nuclear deformation, LINK complex

Mechanical cues during embryogenesis and early development

Keywords: synaptogenesis,

Mechanical cues in disease progression

Keywords: tumor microenvironment, cardiomyopathy

Day 4 Chosen based on invited speakers

Day 5 Summary

grand challenges

potential impacts

future roadmaps

A plan for recruitment of the speakers

The speakers will be selected based on their prior research records and contributions to the field of cell mechanobiology. The steering committee will propose and review the list of names. The final selection will be based on the match between the themes of the workshop and the expertise of the speaker, as well as the diversity of the speakers. Because mechanobiology is a relatively young field and has attracted many new investigators, selection of speakers from the most exciting recent work will inevitably select a relatively young and diverse pool of participants.

Sharing data and outcome of the workshop

The outcome of the workshop will be a report compiling the discussions from the themed sessions and the panels. The report will address the four questions raised by the workshop: (1) The most significant advances in cell mechanobiology to date, (2) The grand challenges and needs of the field, (3) Critical areas of its potential impact, and (4) Roadmaps for the field to realize these potentials. This report will be open to the public and can have a significant impact on the directions of new research by graduate students and junior faculty, as well as on the future funding decisions and allocations of NSF, NSERC, NIH and other institutions, in the US, Canada, and abroad.