From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH): “Scientists unlock nature’s secret to super-selective binding”
11.22.22
Celia Luterbacher
EPFL researchers have discovered that it is not just molecular density, but also pattern and structural rigidity, that control super-selective binding interactions between nanomaterials and protein surfaces. The breakthrough could help optimize existing approaches to virus prevention and cancer detection.
So much of biology comes down to the biophysical process of binding: making a strong connection between one or more groups of atoms – known as ligands – to their corresponding receptor molecule on a surface. A binding event is the first fundamental process that allows a virus to infect a host, or chemotherapy to fight cancer. But binding interactions – at least, our understanding of them – have a ‘Goldilocks problem’: too few ligands on one molecule makes it impossible for it to stably bind with the correct target, while too many can result in undesirable side-effects.
“When binding is triggered by a threshold density of target receptors, we call this “super-selective” binding, which is key to preventing random interactions that could dysregulate biological function,” explains Maartje Bastings, head of the Programmable Biomaterials Laboratory (PBL) in the School of Engineering. “Since nature typically doesn’t overcomplicate things, we wanted to know the minimum number of binding interactions that would still allow for super-selective binding to occur. We were also interested to know whether the pattern the ligand molecules are arranged in makes a difference in selectivity. As it turns out, it does!”
Schematic depicting different types of binding interactions © Bastings/PBL EPFL.
Bastings and four of her PhD students have recently published a study in the Journal of the American Chemical Society that identifies the optimal ligand number for super-selective binding: six. But they also found, to their excitement, that the arrangement of these ligands – in a line, circle, or triangle, for example – also significantly impacted binding efficacy. They have dubbed the phenomenon “multivalent pattern recognition” or MPR.
“MPR opens up a whole new set of hypotheses around how molecular communication in biological and immunological processes might work. For example, the SARS-CoV-2 virus has a pattern of spike proteins that it uses to bind to cell surfaces, and these patterns could be really critical when it comes to selectivity.”
From coronaviruses to cancer
Because its double helix structure is so precise and well understood, DNA is the perfect model molecule for the PBL’s research. For this study, the team designed a rigid disk made entirely out of DNA, where the position and number of all ligand molecules could be precisely controlled. After engineering a series of ligand-receptor architectures to explore how density, geometry, and nano-spacing influenced binding super-selectivity, the team realized that rigidity was a key factor. “The more flexible, the less precise,” Bastings summarizes.
“Our aim was to carve out design principles in as minimalist a way as possible, so that every ligand molecule participates in the binding interaction. What we now have is a really nice toolbox to further exploit super-selective binding interactions in biological systems.”
The applications for such a “toolbox” are far-reaching, but Bastings sees three immediately valuable uses. “Like it or not,” she says, “the SARS-CoV-2 virus is currently a first thought when it comes to virological applications. With the insights from our study, one could imagine developing a super-selective particle with ligand patterns designed to bind with the virus to prevent infection, or to block a cell site so that the virus cannot infect it.”
Diagnostics and therapeutics such as chemotherapy could also benefit from super-selectivity, which could allow for more reliable binding with cancer cells, for which certain receptor molecules are known to have a higher density. In this case, healthy cells would remain undetected, drastically reducing side effects.
Finally, such selectivity engineering could offer key insights into complex interactions within the immune system. “Because we can now play precisely with patterns of what happens at binding sites, we can, in a sense, potentially ‘communicate’ with the immune system,” Bastings says.
Science paper:
Journal of the American Chemical Society
See the science paper for instructive material with images.
See the full article here .
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The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH) is a research institute and university in Lausanne, Switzerland, that specializes in natural sciences and engineering. It is one of the two Swiss Federal Institutes of Technology, and it has three main missions: education, research and technology transfer.
The QS World University Rankings ranks EPFL(CH) 14th in the world across all fields in their 2020/2021 ranking, whereas Times Higher Education World University Rankings ranks EPFL(CH) as the world’s 19th best school for Engineering and Technology in 2020.
EPFL(CH) is located in the French-speaking part of Switzerland; the sister institution in the German-speaking part of Switzerland is The Swiss Federal Institute of Technology ETH Zürich [Eidgenössische Technische Hochschule Zürich] (CH). Associated with several specialized research institutes, the two universities form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles Polytechniques Fédérales] (CH) which is directly dependent on the Federal Department of Economic Affairs, Education and Research. In connection with research and teaching activities, EPFL(CH) operates a nuclear reactor CROCUS; a Tokamak Fusion reactor; a Blue Gene/Q Supercomputer; and P3 bio-hazard facilities.
ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École Polytechnique Fédérale de Lausanne](CH), and four associated research institutes form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.
The roots of modern-day EPFL(CH) can be traced back to the foundation of a private school under the name École Spéciale de Lausanne in 1853 at the initiative of Lois Rivier, a graduate of the École Centrale Paris (FR) and John Gay the then professor and rector of the Académie de Lausanne. At its inception it had only 11 students and the offices were located at Rue du Valentin in Lausanne. In 1869, it became the technical department of the public Académie de Lausanne. When the Académie was reorganized and acquired the status of a university in 1890, the technical faculty changed its name to École d’Ingénieurs de l’Université de Lausanne. In 1946, it was renamed the École polytechnique de l’Université de Lausanne (EPUL). In 1969, the EPUL was separated from the rest of the University of Lausanne and became a federal institute under its current name. EPFL(CH), like ETH Zürich (CH), is thus directly controlled by the Swiss federal government. In contrast, all other universities in Switzerland are controlled by their respective cantonal governments. Following the nomination of Patrick Aebischer as president in 2000, EPFL(CH) has started to develop into the field of life sciences. It absorbed the Swiss Institute for Experimental Cancer Research (ISREC) in 2008.
In 1946, there were 360 students. In 1969, EPFL(CH) had 1,400 students and 55 professors. In the past two decades the university has grown rapidly and as of 2012 roughly 14,000 people study or work on campus, about 9,300 of these being Bachelor, Master or PhD students. The environment at modern day EPFL(CH) is highly international with the school attracting students and researchers from all over the world. More than 125 countries are represented on the campus and the university has two official languages, French and English.
Organization
EPFL is organized into eight schools, themselves formed of institutes that group research units (laboratories or chairs) around common themes:
School of Basic Sciences
Institute of Mathematics
Institute of Chemical Sciences and Engineering
Institute of Physics
European Centre of Atomic and Molecular Computations
Bernoulli Center
Biomedical Imaging Research Center
Interdisciplinary Center for Electron Microscopy
MPG-EPFL Centre for Molecular Nanosciences and Technology
Swiss Plasma Center
Laboratory of Astrophysics
School of Engineering
Institute of Electrical Engineering
Institute of Mechanical Engineering
Institute of Materials
Institute of Microengineering
Institute of Bioengineering
School of Architecture, Civil and Environmental Engineering
Institute of Architecture
Civil Engineering Institute
Institute of Urban and Regional Sciences
Environmental Engineering Institute
School of Computer and Communication Sciences
Algorithms & Theoretical Computer Science
Artificial Intelligence & Machine Learning
Computational Biology
Computer Architecture & Integrated Systems
Data Management & Information Retrieval
Graphics & Vision
Human-Computer Interaction
Information & Communication Theory
Networking
Programming Languages & Formal Methods
Security & Cryptography
Signal & Image Processing
Systems
School of Life Sciences
Bachelor-Master Teaching Section in Life Sciences and Technologies
Brain Mind Institute
Institute of Bioengineering
Swiss Institute for Experimental Cancer Research
Global Health Institute
Ten Technology Platforms & Core Facilities (PTECH)
Center for Phenogenomics
NCCR Synaptic Bases of Mental Diseases
College of Management of Technology
Swiss Finance Institute at EPFL
Section of Management of Technology and Entrepreneurship
Institute of Technology and Public Policy
Institute of Management of Technology and Entrepreneurship
Section of Financial Engineering
College of Humanities
Human and social sciences teaching program
EPFL Middle East
Section of Energy Management and Sustainability
In addition to the eight schools there are seven closely related institutions
Swiss Cancer Centre
Center for Biomedical Imaging (CIBM)
Centre for Advanced Modelling Science (CADMOS)
École Cantonale d’art de Lausanne (ECAL)
Campus Biotech
Wyss Center for Bio- and Neuro-engineering
Swiss National Supercomputing Centre
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