D1. Knowledge and Understanding: At the end of the course, the student must demonstrate having acquired the fundamental principles of biophysics, with particular reference to molecular biophysics, membrane biophysics, and cellular biomechanics. The student must also understand both qualitative and quantitative aspects of the experimental techniques used in these fields, such as Atomic Force Microscopy, Optical Tweezers, Magnetic and Acoustic Tweezers, Electron Microscopy, Vibrational Microscopy, Super-Resolution Optical Microscopy, and X-ray Diffraction and Scattering. D2. Ability to Apply Knowledge and Understanding: At the end of the course, the student must be able to apply the knowledge acquired in point D1 to hypothesize biophysics experiments with the introduced techniques, discuss and analyze in detail the experimental data provided in order to independently interpret the experiment results. The student must know the statistical rules for interpreting biological results and be able to apply significance tests to the data. D3. Autonomy of Judgment: At the end of the course, the student will be able to evaluate the experimental methods discussed in various contexts, judge which is most appropriate for studying the mechanical properties of biological systems with different rigidity, size, and corrugation, and critically evaluate the literature articles on these topics that will be proposed. D4. Communication Skills: At the end of the course, the student must demonstrate having acquired the basic concepts referred to in point D1, as well as appropriate language to precisely discuss various biophysics topics. The student must be able to critically and constructively judge the topics covered in the course. D5. Learning Skills: At the end of the course, the student must be able to show an adequate level of understanding of the topics covered, be able to critically read published works in specialized journals in the field, and evaluate the proposed techniques on specific systems in a comparative manner, highlighting the quantitative aspects of the experiments.

The students are not required to have followed any specific course. Knowledge of basic solid mechanics and statistical mechanics could be an advantage.

The course aims to introduce students to the concepts, formalisms, methodologies, and tools of physics that have significant applications in biology and medicine. The goal is to demonstrate how describing living systems in terms of complex physical systems complements more traditional experimental investigations. The course is therefore designed to guide students through interdisciplinary work at the intersection of physics, biology, biochemistry, and nanotechnology. It will expose them—also through the discussion of key research articles in the field of molecular and cellular biophysics—to potential future research paths in the field. Specifically, after an introduction to the structure and function of various macromolecules, the course will touch upon the physics of biopolymers and the intermolecular forces that drive structure and processes such as self-assembly, fibrillation, and protein folding, as well as protein-ligand interactions and molecular bio-recognition. In the second part, after reviewing the main concepts of solid mechanics, fluid dynamics, and statistical mechanics—and introducing essential notions of cellular biology and biochemistry, with a focus on the structure of the plasma membrane and its interaction with the extracellular matrix—the course will concentrate on key aspects of cellular mechanics. It will describe phenomena such as adhesion, migration, and mechanotransduction, which regulate many vital functions of cells and higher organisms, even in pathological context as cancer. The topics covered will be illustrated with examples of experiments drawn from the scientific literature and from the instructor’ own research activities. On this occasion, modern experimental techniques applied to biophysics will be presented in detail. As an integral part of the course, two visits will be organized to the laboratories in Basovizza, where students will have the opportunity to discuss the details of a planned experiment with a tutor, in coordination with the course instructor.

1. J. Howard, Mechanics of Motor Proteins and the Cytoskeleton, Sinauer Associates Inc., 2001
2. B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter, Molecular Biology of the Cell, 4th edition, New York: Garland Science; 2002.
3. D. Boal, Mechanics of the Cell, Cambridge Univ. Press, 2012
4. C.R. Jacobs, H. Huang, R. Y. Kwon, Introduction to Cell Mechanics and Mechanobiology, Garland Science Taylor & Francis, 2013.
5. J.N. Israelachvili, Intermolecular and Surface Forces, Elsevier, Third edition 2011.
6. Scientific articles – pdf collection; cited with the slides associated to the lectures.
7. Slides presentation for the lectures, pdf.

First part – Fundaments of molecular biophysics. 1. Introduction to cellular biophysics and biomolecules. Self-assembling and inter-molecular forces (2h) 2. Proteins: structure, shape and function. The folding-structure problem. Protein folding/unfolding and protein fibers. Membrane proteins (4h) 3. Nucleic Acids: structure, transmission of genetic information, basic genetic engineering; other biopolymers (4h) 4. Structure and transport in cell membrane. Ions in water, ion and molecular transport through the membrane. Formation of extracellular vesicles. Cell signalling (2h) 5. Techniques to study macromolecules structure/function (4h): Optical spectroscopies (fluorescence, IR, Raman) X-ray Crystallography ElectronMicroscopy NMR 6. Protein-ligand equilibrium interactions; biochemical kinetics; techniques used (Surface plasmon resonance, calorimetry) (2h) 7. Biosensors (2h) 8. Single molecule interactions and relative techniques (FRET, Foster Resonant Energy Transfer, Atomic Force Microscopy, Coherent X-ray diffraction (2h) Secon part – Cellular mechanics and mechano-biology. 1. Introduction to mechano-biology (2h) 2. Physical principles (8h) 2.1. Mechanical forces, viscoelasticity at molecular and cell level 2.2. Thermal forces and diffusion 2.3. Chemical forces 2.4. Motor proteins (types, working principles) 3. Mechanics of the Cytoskeleton (4h) 3.1. Cytoskeleton structure 3.2. Force generation by the cytoskeleton and cell motility 4. Cellular Mechanotransduction (2h) 5. Experimental techniques – for cell mechanics (6h) 5.1. Overview on force application and force sensing techniques 5.2. Optical Tweezers – force spectroscopy and manipulation 5.3. Magnetic and Acoustic Tweezers 5.4. Advanced Optical Microscopy techniques (Super-Resolution, FRET, DHM) Third part – Experimental activity 1. Small groups experimental activities, on two topics from part one and two of the course, respectively (4+4h)

Lectures and lab experiences under the teacher’s guide.

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Oral exam. The exam will mainly focus on a discussion component, involving a discussion of two articles assigned by the instructor five days before the oral exam, each relating respectively to one topic from the first part of the course and one from the second part. Questions may cover the entire syllabus, and will refer to the learning objectives described above. The evaluation will be based on the following criteria: - Excellent (30–30 cum laude): Outstanding knowledge of the topics, excellent command of language, excellent analytical skills; the student is able to brilliantly apply theoretical knowledge to practical cases. - Very Good (27–29): Good knowledge of the topics, notable command of language, good analytical skills; the student is able to correctly apply theoretical knowledge to practical cases. - Good (24–26): Good knowledge of the main topics, fair command of language; the student demonstrates adequate ability to apply theoretical knowledge to practical cases. - Satisfactory (21–23): The student does not demonstrate full mastery of the main course topics, though they possess basic knowledge; they still show satisfactory command of language and sufficient ability to apply theoretical knowledge to practical cases. - Sufficient (18–20): Minimal knowledge of the main course topics and technical language, limited ability to adequately apply theoretical knowledge to practical cases. - Insufficient (<18): The student does not possess an acceptable understanding of the content across the various course topics.

This course delves into topics that are closely related to one or more of the goals of the United Nations 2030 Agenda for Sustainable Development.