Complex rheology in biological systems

The gastrointestinal (GI) tract actively transports food along different organs to mix it with secretions and break down food particles, which can then be absorbed by the body while waste is eliminated. This involves a variety of biological, chemical, and physical phenomena. Understanding flow phenomena in the GI tract is important for human health, as it can impact drug delivery, the spatiotemporal organisation of the microbiota, and lead to health problems related to GI motility dysfunction. This presentation demonstrates how the gastrointestinal tract handles complex flow by providing two examples: one at the organ scale and the other at the microscopic scale.

The first example aims to demonstrate how complex fluid dynamics modelling of video defecography can aid in diagnosing defecation disorders. A two-dimensional patient-specific simulation was developed based on standard X-ray video defecographies to quantify velocity, pressure, and stress fields during defecation for patients with normal and pathological defecatory function. The results showed that normal defecation involved a proximal–distal pressure gradient from both the anorectal junction and the anal canal, with the flow dominated by shear-thinning viscous properties. Impaired defecations were also simulated and compared to normal defecation, leading to a discussion of critical factors that could aid in effective medical management.

In the second example, the focus is on how fluid is transported and mixed at small scales using microscopic finger-like structures, the so-called villi. A numerical model was developed to simulate flow and mixing due to the active movement of villi. By using the physiological pattern of contractions, it was shown that villi can either transport fluid in the longitudinal direction of the small intestine and/or induce radial mixing. These phenomena are due to a combination of geometric effects (wave propagation) and inertia at moderate Reynolds number.

Dr Clement de Loubens, Université Grenoble Alpes, France

Dr Clement de Loubens, Université Grenoble Alpes, France

Clément de Loubens is a CNRS researcher based at Laboratoire Rhéologie et Procédés, part of the University of Grenoble Alpes. He has been working at CNRS since 2016 and has extensive experience in the field of complex fluid flows and soft matter physics, particularly those related to the digestive system. Clément has made significant contributions to our understanding of how complex fluids behave in the digestive system. His research involves using a combination of experimental and numerical approaches to investigate the flow and mixing of non-Newtonian fluids in the human digestive tract, both at the organ scale and at the microstructure level of the intestinal mucosa. Through his research, Clément de Loubens has shed light on the role of active microstructure, the so-called villi, in mixing and the importance of non-Newtonian properties of human feces in defecation problems.

Mucus is a viscoelastic fluid that participates to the protective barrier of many mammals' epithelia. In the airways, together with cilia beating, mucus rheological properties are crucial for lung mucociliary function, and, when impaired, potentially participate to the onset and progression of chronic pulmonary diseases. Human bronchial epithelium (HBE) cultures are highly reliable models to assess non contaminated mucus.

Hallmarks of shear-thinning and elasticity are obtained at the macroscale whereas at the micro-scale, HBE mucus appears as a heterogeneous medium showing an almost Newtonian behaviour in some extended regions and an elastic behaviour and adhesion forces close to boundaries. Finally, Dr Massiera reports an original method to measure mucus microrheology directly on the tissue culture using optical tweezers, showing that mucus gradually varies in rheological response, from an elastic behaviour close to the epithelium to a viscous one far away. Taken together, all these results collectively support a structure composed of a network of elastic adhesive filaments with a large mesh-size, embedded in a very soft gel.

Dr Gladys Massiera, Université de Montpellier, France

Dr Gladys Massiera, Université de Montpellier, France

Gladys Massiera is a professor of the University of Montpellier, in Laboratoire Charles Coulomb. She completed a PhD in Physics in 2002 in the field of soft condensed matter and a post-doctoral research (2002-04) at the University of Pennsylvania, on cell mechanics. In 2004, she became assistant professor from the University of Grenoble and developed new research activities using biomimicry to understand cellular flow and adhesion. After joining the University of Montpellier in 2006, she patented a now widely used microencapsulation process. She also studied red blood cells, deciphering some aspects of parasites release and interactions with flow in the specific case of sickle cell anemia genetic disease. She became a professor in 2017. Over the last 8 years, her research has been focused on the physical aspects of the muco-ciliary function; mucus rheology and synchrony in cilia beating for mucus flow in collaboration with physicians and biologists from Montpellier.

Bacterial spreading via motility and growth plays a central role in agriculture, biotechnology, the environment, and medicine. These processes are typically studied in the lab in liquid cultures or on flat surfaces. However, many bacterial habitats, eg soils, sediments, and biological gels/tissues, are more complex and crowded 3D spaces. In this talk, Professor Datta will describe his group's work using tools and approaches from soft matter and rheology, imaging, and biophysical modelling to unravel how life in a complex 3D space influences how bacteria spread. He has developed the ability to (i) directly visualise bacteria from the scale of a single cell to that of an entire population, and (ii) 3D-print precisely structured multi-cellular communities, in crowded 3D media more akin to their natural habitats. His experiments using this platform have revealed previously unknown ways in which living in a complex space fundamentally alters how bacteria move and grow, both at the single cell and population scales. Moreover, our results indicate that bacterial colonies can be modelled as 'active fluids' whose rheology is governed by the coupling between cellular motility, growth, and external chemical signals. This provides new ways to predict and control the organisation of bacteria, and other forms of 'active matter', in complex environments more accurately. These findings could also potentially help provide quantitative guidelines for the control of these dynamics in processes ranging from bioremediation and agriculture to drug delivery.

Professor Sujit Datta, Princeton University, USA

Professor Sujit Datta, Princeton University, USA

Sujit Datta is an Associate Professor and Director of Graduate Studies of Chemical and Biological Engineering at Princeton University. He earned a BA in Mathematics and Physics and an MS in Physics in 2008 from the University of Pennsylvania, and then a PhD in Physics in 2013 from Harvard, where he studied fluid dynamics and instabilities in soft and disordered media with Dave Weitz. His postdoctoral training was in Chemical Engineering at Caltech, where he studied the biophysics of the gut with Rustem Ismagilov. Datta joined Princeton in 2017, where his lab studies the dynamics, self-organisation, and applications of complex, soft ('squishy'), and living systems. Datta’s research has revealed and shed new light on the fascinating behaviours manifested by complex fluids and bacterial populations in complex environments, guiding the development of new approaches to environmental remediation, energy production, agriculture, water security, and biotechnology. He also actively leads outreach efforts in STEM to bring together diverse perspectives and provide access to researchers from traditionally under-represented groups in studies of soft and living systems. Datta’s scholarship has been recognized by awards from a broad range of different communities, reflecting its multidisciplinary nature, including through the AIChE 35 Under 35 Award, ACS Unilever Award, Camille Dreyfus Teacher-Scholar Award, three awards from the APS (Early Career Award in Biological Physics, Andreas Acrivos Award in Fluid Dynamics, and the Apker Award), the Arthur Metzner of the Society of Rheology, Pew Biomedical Scholar Award, NSF CAREER Award, and multiple commendations for teaching. 

How do cells sense and respond to the mechanical stress generated by their own growth? How do they achieve a finite and stable size of the organ they form? These are fundamental questions in biorheology that have implications for development, homeostasis and disease. In this talk, Dr Erlich will present a novel continuum model that incorporates an energetic cost of growth into the morphoelastic framework. This model allows for a local feedback mechanism between growth and stress that leads to size control of growing tissues. This feedback mechanism is called a continuum 'growth law', a rheological law that models growth analogously to plastic flow. He will apply this model to multicellular spheroids, which are spherical aggregates of cells that mimic some aspects of solid tumours. Dr Erlich will show how the model can reproduce the experimentally observed features of spheroids, such as residual stress, necrotic core and growth arrest. He will also discuss how the model can be used to explore the effects of different parameters and boundary conditions on the spheroid dynamics. This work demonstrates the importance and usefulness of rheological methods and models for understanding complex biological systems. 

Dr Alexander Erlich, Université Grenoble Alpes, France

Dr Alexander Erlich, Université Grenoble Alpes, France

Alexander Erlich is an applied mathematician who investigates how mechanics shapes and regulates living biological systems. He is currently a CNRS researcher at the Laboratoire Interdisciplinaire de Physique in Grenoble, France, where he focuses on modelling growth in living elastic tissues. He is especially interested in how feedback laws between growth, mechanical stress, and chemical fields determine the final size of an organism. Alexander obtained his PhD in non-linear elasticity and growth from the University of Oxford, where he worked with Alain Goriely and Derek E Moulton. He then did post-docs in fluid mechanics and transport at the University of Manchester, cell motility at LiPhy (Grenoble), and developmental biology at CENTURI (Marseille). His publications include topics such as growth-induced instabilities, placental transport, tissue folding, tumour spheroids, water lilies and Ammonites’ shells. He also collaborates with experimental biologists and physicists to test and validate his models.

Bacterial biofilms generate their own internal stresses by growth and production of exopolysaccharides (EPS). A central question seems to be how these bacterial colonies reconcile the mechanical strength to protect themselves from the access to nutrients. Professor Vermant focuses on colonies which generate a significant amount of EPS. A first challenge he will address is to measure the rheological properties in situ, either macroscopically or using active microrheological measurement. Second, Professor Vermant will discuss the relevance of the rheological properties and their time evolution in the development and transport phenomena within the biofilm.

Professor Jan Vermant, ETH Zürich, Switzerland

Professor Jan Vermant, ETH Zürich, Switzerland

Dr Vermant studied Chemical Engineering at KU Leuven in Belgium, obtaining the doctoral degree in 1996 under the supervision of Professor Jan Mewis. He was a postdoctoral fellow of Elf Aquitaine (Stanford) and the Fund for Scientific Research – Vlaanderen. In 2000 he joined the faculty at the department of Chemical Engineering at KU Leuven, becoming a full professor in 2005. In 2014 he joined the Materials Department at the ETH Zürich where he now heads the laboratory of Soft Materials. He has held visiting appointments at Stanford University (USA), University of Delaware (USA), Princeton University (USA), the Forschungszentrum Jülich (G) and the ESPCI (F). His research at the ETH Zürich focuses on the rheology and applications of complex fluid-fluid interfaces, colloidal suspensions and the development of novel experimental methods and soft matter applications in materials science.

Biofilms are aggregates of microorganisms in which cells are embedded in a self-secreted matrix of polymeric substances, which protects the microbial community from chemical and mechanical insults, thus favouring its survival and evolutionary success. As a result, biofilms have a crucial impact in environmental, industrial, and medical settings. Despite this, there is a severe lack of understanding of how the environment shapes biofilms’ physico-chemical properties and, in turn, how their characteristics drive their response to environmental conditions. 

Dr Secchi investigates how environmental conditions drive biofilm assembly and the emergence of distinctive morphological and rheological properties. In particular, she focuses on fluid flow, given its ubiquities in the aquatic habitats where biofilms are found. Flow can influence several stages of biofilm formation, starting from surface colonisation. On curved surfaces, flow can promote the formation of colonisation hotspots, which lately impact biofilm formation. Surface geometry, flow shear, fluid rheology, and bacterial phenotype are the parameters controlling surface colonisation. She will also show that during biofilm maturation in porous systems, the interplay between biological functions, ie growth, and physics mechanisms, ie flow shear stress, controls biofilm morphology, rheology, and ultimately affects the physiological protective function of biofilms. By shedding light on this interplay, we can control biofilm development, showing the prominent role that physics can play in developing novel antifouling strategies. 

Dr Eleanora Secchi, ETH Zurich, Switzerland

Dr Eleanora Secchi, ETH Zurich, Switzerland

Dr Eleonora Secchi is the Group Leader of the bioMatter Microfluidics Group at ETH Zurich, Switzerland. After earning her PhD from the Polytechnic University of Milan, she was a postdoctoral fellow at Ecole Normale Supérieure of Paris, working on measuring water flow from a single carbon nanotube. She was awarded an ETH Postdoctoral Fellowship in 2016. In 2018, thanks to a Swiss National Science Foundation PRIMA grant, Dr Secchi started her research group. Her research aims to understand the physical mechanisms and environmental factors controlling bacterial surface colonisation and biofilm formation. Biofilms are a widespread mode of growth of bacteria and have a crucial impact in environmental, industrial, and medical settings. She brings to this critical problem an interdisciplinary, cutting-edge toolbox: by applying tools from microfluidics, fluid dynamics, microbial ecology, and soft matter physics to characterise biofilm formation and rheology, she seeks to understand their behaviour and impact in natural and industrial systems.

Cytoskeleton plays a critical role in the cell shape, locomotion, growth, and division in response to the surrounding environment. Since it may be affected by diseases and drugs, quantification of the rheological cell properties can help understanding their impact. In this study, the breast cancer cell line MCF-7 was treated with different concentrations of microtubule-active drugs. The cell vitality over 90% was possible to obtain in the concentration range far beyond the cytotoxicity level by treating the cells with low concentration of hydroxyurea prior to the drugs treatment. The stiffness of the drug treated cells in a monolayer was measured by a modified narrow-gap rheometer. With a precision for its gap error better than ±0.4μm, it allows detecting in oscillation the viscoelastic response of cells fixed to both rheometer plates at gap widths of micrometer scale down to the linear viscoelastic regime. With known cell coverage, the average cell moduli can be determined from single experimental runs. Studying the impact of bubbles and dust shows that these error sources have no significant impact on our data. Ms Lee found that the gap width has a strong impact on normal force and storage and loss moduli. She observed two regimes depending on the gap width, apparently caused by the cells’ nuclei and cytoskeleton. Yet, no clear impact of the microtubule-active drugs was observed in the linear viscoelastic range.

Ms Suhyang Lee, LSTME Busan Branch, South Korea, and Friedrich-Alexander Universität Erlangen-Nürnberg, Germany

Ms Suhyang Lee, LSTME Busan Branch, South Korea, and Friedrich-Alexander Universität Erlangen-Nürnberg, Germany

Ms Suhyang Lee holds a Master of Science in chemical and bio engineering from Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany. Her Masters' thesis focused on the topic of Light Distribution in Photo-bioreactor, where she simulated the light propagation with the application of geometrical optics. She is currently in a doctoral course at the Institute of Fluid Mechanics at FAU. With the interest of biomatter, she is studying cell rheology under the supervision of Professor Andreas Wierschem. Additionally, she is a full-time researcher at the biorheology group at LSTME-Busan Branch, a German engineering research and development centre in Busan, South Korea.