Cellular and molecular mechanobiology


About

Every time we blink, move a hand, draw a breath, or walk, cells in our body exert, transmit, withstand, and detect forces. This mechanical interaction with the environment determines how cells proliferate, differentiate, and move, and regulates development, tumorigenesis or wound healing.

Artistic rendering of a cell attaching to a substrate coated with a gold nano-pattern array, used to study how cells detect spatial cues (From Oria et al. 2017, Nature)

Just like biochemical stimuli initiate signaling cascades, mechanical forces affect the links and conformation of a network of molecules connecting cells to the extracellular matrix. Our research aims precisely at unraveling the mechanisms that these molecules use to detect and respond to mechanical stimuli like forces or tissue rigidity, triggering downstream cell responses. To this end, we combine biophysical techniques like magnetic tweezers, Atomic Force Microscopy, traction microscopy, and microfabricated force sensors with molecular biology, advanced optical microscopy, and theoretical modelling.

Sensing rigidity: Using this multi-disciplinary approach, we have recently unveiled a molecular mechanism that cells employ to detect and respond to the rigidity of their environment, which could be crucial in breast tissue and breast cancer (Elosegui-Artola et al., 2016 Nat. Cell Biol., and Elosegui-Artola et al. 2014, Nature Mater.). This mechanism is mediated by what is known as a “molecular clutch”: in a surprising analogy with a car engine, cells can be understood as a molecular network that can engage and disengage from its environment, just as the clutch of a car. This affects force transmission from the environment to cells, and also within different cell components. Recently, we have begun to explore how force transmission to the nucleus affects the dynamics of transcriptional regulators, such as YAP (Elosegui-Artoal et al., 2017, Cell).

Cartoon depicting how force transmission to the nucleus affects nuclear pores, leading to nuclear protein import (from Elosegui-Artola et al. 2017, Cell)

Sensing the environment: We are currently expanding on the idea of the molecular clutch, to explore how cell molecular engines sense not only mechanical rigidity, but other important parameters from their environment: for instance, the composition and distribution of ligands in the extracellular matrix, or other cells. In this regard, we recently uncovered that this concept can explain how cells sense the spatial distribution of ligands in the extracellular matrix (Oria et al., Nature 2017). We have also demonstrated that cell-cell force transmission, mediated by a molecular clutch, is essential for cells to sense gradients in stiffness (Sunyer et al., Science 2016, in collaboration with the group of Xavier Trepat).

The membrane as a mechanosensor: Due to its mechanical properties, the plasma membrane itself can respond to forces and act as a mechanosensor. Recently, we have shown that cell membranes can use purely physical principles to adapt their shape in response to mechanical forces (Kosmalska et al., 2015, Nat. Commun.). We are currently studying how cells harness this physical membrane behavior to respond to signals from their environment.

Ultimately, when we determine the molecular mechanisms that communicate cells with their environment, we will understand how forces determine development when things go right, and tumor formation when they go wrong.

 

Video: How tissue stiffness activates cancer

 

Staff

Pere Roca-Cusachs Soulere | Group Leader
Ion Andreu Arzuaga | Postdoctoral Researcher
Amy Beedle | Postdoctoral Researcher
Alberto Elosegui Artola | Postdoctoral Researcher
Laura Faure | Postdoctoral Researcher
Zanetta Zoi (Jenny) Kechagia | Postdoctoral Researcher
Anabel-Lise Le Roux | Postdoctoral Researcher
Ignacio Viciano Gonzalo | Postdoctoral Researcher
Ignasi Granero Moya | PhD Student
Marc Molina Jordán | PhD Student
Marina Pavlova | PhD Student
Xarxa Quiroga Álvarez | PhD Student
Srivatsava Viswanadha Venkata Naga Sai | PhD Student
Miguel González Martín | Research Assistant
Susana Usieto Camín | Laboratory Technician
Aurora Dols Pérez | Visiting Researcher

 


 

Projects

European projects
MECHANOCONTROL · Mechanical control of biological function (2017-2021) European Commission, FET Proactive Pere Roca-Cusachs
TALVIN · Inhibiting mechanotransduction for the treatment of pancreatic cancer (2018-2020) European Commission, FET Innovation Launchpad Pere Roca-Cusachs
National projects
Desarrollo de una terapia innovadora para el tratamiento de los tumores sólidos mediante la inhibición de la mecanotransducción (2018-2020) MINECO, Subprograma Retos-Colaboración Pere Roca-Cusachs
IMREG El sistema acoplado entre integrinas y proteínas adaptadoras como regulador mecánico del comportamiento celular (2016-2020) MINECO, Proyectos I+D Excelencia Pere Roca-Cusachs
Privately-funded projects
Understanding and measuring mechanical tumor properties to improve cancer diagnosis, treatment, and survival: Application to liquid biopsies (2017-2020) Obra Social La Caixa Pere Roca-Cusachs
Finished projects
MECHANOMEMBRANE Redes mecanoquímicas en la membrana plasmática (2017-2018) MINECO, Subprograma Estatal de Generación de Conocimiento “EUROPA EXCELENCIA” Pere Roca-Cusachs
Stromal stiffness in tumor progression (2014-2017) Fundació La Marató de TV3 Pere Roca-Cusachs
MECBIO Red de Excelencia en Mecanobiología (2014-2016) MINECO, Subprograma Estatal de Generación de Conocimiento “REDES DE EXCELENCIA” Pere Roca-Cusachs
Inhibiting mechanostransduction as a novel therapy in the treatment of solid tumors (2017-2018) Obra Social La Caixa Pere Roca-Cusachs

 

Publications

Click here for a list of publications by Pere Roca-Cusachs with IBEC affiliation.

Click here for a full list of publications including those affiliated to other organisations.

Equipment

  • Confocal Microcopy
  • Traction Microscopy
  • Live cell fluorescence microscopy
  • Cell stretching
  • Cell culture
  • Magnetic Tweezers
  • Atomic Force Microscopy
  • Surface Micro/Nano-patterning
  • Optical tweezers

Collaborations

  • Dr. Nils Gauthier
    Mechanobiology Institute, Singapore
  • Prof. Miguel Ángel del Pozo
    Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid
  • Prof. Marino Arroyo
    UPC, Barcelona
  • Prof. Ada Cavalcanti
    University of Heidelberg, Germany
  • Satyajit Mayor
    National Centre for Biological Sciences, Bangalore, India
  • Sergi Garcia-Manyes
    King’s College, London, UK
  • Cheng Zhu
    Georgia Tech, Atlanta, USA
  • Louise Jones
    Barts Cancer Institute, London, UK

 

News/Jobs

L’investigador Pere Roca-Cusachs entra al club de l’elit europea en biologia

Pere Roca-Cusachs, investigador principal de l’Institut de Bioenginyeria de Catalunya (IBEC) i professor agregat de la Facultat de Medicina de la Universitat de Barcelona (UB), ha estat escollit per formar part de la prestigiosa EMBO, l’Organització Europea de Biologia Molecular, que agrupa alguns dels investigadors més brillants del món.

Roca-Cusachs és un pioner en el camp de la mecanobiologia i l’estudi de com les forces físiques afecten processos com el càncer.

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Gran èxit de l’escola d’estiu “Mecanobiologia del Càncer 2019” organitzada pel projecte Mechano·Control

Més de 60 persones van assistir a l’escola d’estiu “Mecanobiología del Càncer 2019” organitzada per l’IBEC, ja que el centre és el coordinador del projecte Mechano·Control. L’escola d’estiu es va celebrar a Prullans, un petit poble situat als Pirineus catalans entre el 17 i el 21 de setembre. L’esdeveniment va ser un gran èxit tant en participació com en l’àmbit científic. L’objectiu de l’escola d’estiu era proporcionar capacitació en mecanobiología, i específicament la seva aplicació al càncer de mama, i promoure les interaccions entre professionals del camp.

L’escola va incloure conferències i tallers pràctics sobre diferents tècniques i disciplines, des de la biomecànica fins a la biologia del càncer. El projecte Mechano·Control, coordinat per Pere Roca-Cusachs, investigador principal de l’IBEC, és el projecte europeu més gran coordinat per la institució fins a dia d’avui.

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L’últim ‘Insight’ de Nature Physics presenta un article IBEC/Crick

L’investigador principal de l’IBEC i professor de recerca ICREA Xavier Trepat ha publicat una ressenya a l’edició ‘Insight: The Physics of Living Systems’ de Nature Physics, en el qual tots els articles han estat co-escrits per un físic i un biòleg.

Escrit amb el seu col·laborador Erik Sahai de l’Institut Francis Crick de Londres, l’article de Trepat, “Mesoscale physical principles of collective cell organization”, revisa la recent evidència que la dinàmica cel·lular i tissular es regeix per principis físics en la mesoescala: força, densitat, forma, adhesió i autopropulsió.

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Les forces físiques regulen la divisió cel·lular

Investigadors de l’IBEC ha descobert que la divisió cel·lular que es produeix en teixits epitelials està regulada per forces mecàniques

Aquest descobriment obre la porta a una major comprensió de la proliferació descontrolada de les cèl·lules canceroses en els tumors, i a la seva possible regulació per mitjà de forces físiques.

El resultat de la recerca, que s’ha publicat a la revista Nature Cell Biology, ha estat duta a terme pel grup de recerca del Xavier Trepat, professor ICREA a l’IBEC i professor associat a la UB, i en ella es relaciona l’estat mecànic del teixit amb la progressió al llarg del cicle cel·lular i divisió de les seves cèl·lules.

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