Biotechnology

Cellular Mechanobiology

Mechanobiology

Cell Biology

Intracellular Signaling

Stem Cells

Cell Fate Decisions

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Leader

Mário Grãos

Researcher


Research lines

Oligodendrocyte mechanobiology and multiple sclerosis

Neuronal mechanotransduction and Alzheimer’s disease

Molecular mechanisms underlying mechanotransduction in mechanosensitive cells

Mechanomodulation of MSC during reprogramming and differentiation

Mechanomodulation of the MSC proteome

Overview

Our research interest is Cellular Mechanobiology. We are currently focused on the implications & molecular mechanisms underlying mechanical modulation of neural cells and mesenchymal stem/stromal cells (MSCs).

We develop cell-culture platforms with defined biochemical and mechanical features mimicking physiological or pathological properties of the extracellular matrix, being usable for a wide range of cells, conditions and applications.


Mechanobiology of neural cells

It was reported that CNS diseases like Multiple Sclerosis (MS) or Alzheimer’s disease (AD) are accompanied by changes in the mechanical properties of the brain.

We showed that oligodendrocytes are highly mechanosensitive cells (doi:10.3389/fncel.2016.00277, doi: 10.1038/srep21563), being currently elucidating its underlying molecular mechanisms, aiming to understand specific aspects of oligodendrocyte biology and disease (particularly MS) and to exploit mechanobiology-based screening platforms to study novel therapeutic agents.

We are also exploring mechanotransduction in a context of AD, by targeting specific intracellular mechanisms involved in the disease identified as being regulated by mechanosignalling, hence elucidating its fundamental mechanisms and exploiting future therapeutic opportunities.


Mechanomodulation of MSCs

MSCs are adult progenitor cells with extensive self-renewal and differentiation capacity (doi:10.1371/journal.pone.0111059), holding a great potential for cell-based clinical applications. MSCs also provide important trophic and immunomodulatory factors that may contribute to tissue regeneration and regulation of inflammation & immunity.

We are tackling the mechanomodulation of MSCs during reprogramming (doi:10.1038/s41598-019-45352-3) and differentiation towards clinically-relevant lineages. We are also elucidating the molecular mechanisms underlying the response of MSCs to mechanical cues and its influence in the MSC proteome, as well as exploitation of future clinical applications.

Publications

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Information about journal articles, updated at 25-07-2021, from platform CIÊNCIAVITAE.

Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

Inês Serrenho; Miguel Rosado; Alexandra Dinis; Carla M. Cardoso; Mário Grãos; Bruno Manadas; Graça Baltazar, 2021. International Journal of Molecular Sciences. 3142 - 3142. 6. 22. 2021. https://doi.org/10.3390/ijms22063142 . 10.3390/ijms22063142 . International Journal of Molecular Sciences

Induced pluripotent stem cell-derived vascular networks to screen nano-bio interactions.

Estronca L; Francisco V; Pitrez P; Honório I; Carvalho L; Vazão H; Blersch J; et al, 2021. Nanoscale horizons. 2021. http://europepmc.org/abstract/med/33576750 . 10.1039/d0nh00550a . Nanoscale horizons

Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury

Floriddia, Elisa M.; Lourenço, Tânia; Zhang, Shupei; van Bruggen, David; Hilscher, Markus M.; Kukanja, Petra; Gonçalves dos Santos, João P.; et al, 2020. Nature Communications. 1. 11. 2020. http://dx.doi.org/10.1038/s41467-020-19453-x . 10.1038/s41467-020-19453-x . Nature Communications

Cofilin-1 Is a Mechanosensitive Regulator of Transcription

Domingues, Catarina; Geraldo, A. Margarida; Anjo, Sandra Isabel; Matos, André; Almeida, Cláudio; Caramelo, Inês; Lopes-da-Silva, José A.; et al, 2020. Frontiers in Cell and Developmental Biology. 8. 2020. http://dx.doi.org/10.3389/fcell.2020.00678 . 10.3389/fcell.2020.00678 . Frontiers in Cell and Developmental Biology

A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers

Anjo, Sandra I.; dos Santos, Patrícia Valério; Rosado, Luiza; Baltazar, Graça; Baldeiras, Inês; Pires, Diana; Gomes, Andreia; et al, 2020. Translational Neurodegeneration. 1. 9. 2020. http://dx.doi.org/10.1186/s40035-020-00188-0 . 10.1186/s40035-020-00188-0 . Translational Neurodegeneration

Use of recombinant proteins as a simple and robust normalization method for untargeted proteomics screening: exhaustive performance assessment

Anjo, Sandra Isabel; Simões, Isaura; Castanheira, Pedro; Grãos, Mário; Manadas, Bruno, 2019. Talanta. 205. 2019. http://dx.doi.org/10.1016/j.talanta.2019.120163 . 10.1016/j.talanta.2019.120163 . Talanta

Soft culture substrates favor stem-like cellular phenotype and facilitate reprogramming of human mesenchymal stem/stromal cells (hMSCs) through mechanotransduction.

Gerardo H; Lima A; Carvalho J; Ramos JRD; Couceiro S; Travasso RDM; Pires das Neves R; Grãos M, 2019. Scientific reports. 2019. http://europepmc.org/abstract/med/31235788 . 10.1038/s41598-019-45352-3 . Scientific reports

oxSWATH: An integrative method for a comprehensive redox-centered analysis combined with a generic differential proteomics screening

Sandra I. Anjo; Matilde N. Melo; Liliana R. Loureiro; Lúcia Sabala; Pedro Castanheira; Mário Grãos; Bruno Manadas, 2019. Redox Biology. 101130 - 101130. 2019. https://doi.org/10.1016/j.redox.2019.101130 . 10.1016/j.redox.2019.101130 . Redox Biology

Modulation of oligodendrocyte differentiation by mechanotransduction

Lourenço, T.; Grãos, M., 2016. Frontiers in Cellular Neuroscience. NOV2016. 10. 2016. http://www.scopus.com/inward/record.url?eid=2-s2.0-85007417961&partnerID=MN8TOARS . 10.3389/fncel.2016.00277 . Frontiers in Cellular Neuroscience

Modulation of oligodendrocyte differentiation and maturation by combined biochemical and mechanical cues

Lourenço, T.; Paes De Faria, J.; Bippes, C.A.; Maia, J.; Lopes-Da-Silva, J.A.; Relvas, J.B.; Graõs, M., 2016. Scientific Reports. 6. 2016. http://www.scopus.com/inward/record.url?eid=2-s2.0-84958568082&partnerID=MN8TOARS . 10.1038/srep21563 . Scientific Reports

Lysophosphatidic acid enhances survival of human CD34+ cells in ischemic conditions

Kostic, I.; Fidalgo-Carvalho, I.; Aday, S.; Vazão, H.; Carvalheiro, T.; Grãos, M.; Duarte, A.; et al, 2015. Scientific Reports. 5. 2015. http://www.scopus.com/inward/record.url?eid=2-s2.0-84946935547&partnerID=MN8TOARS . 10.1038/srep16406 . published Scientific Reports

Dose-dependent inhibition of BACE-1 by the monoterpenoid 2,3,4,4-tetramethyl-5-methylenecyclopent-2-enone in cellular and mouse models of Alzheimer's disease

Videira, R.; Castanheira, P.; Grãos, M.; Resende, R.; Salgueiro, L.; Faro, C.; Cavaleiro, C., 2014. Journal of Natural Products. 1275 - 1279. 6. 77. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84903648214&partnerID=MN8TOARS . 10.1021/np400903w . Journal of Natural Products

Differentiation of human umbilical cord matrix mesenchymal stem cells into neural-like progenitor cells and maturation into an oligodendroglial-like lineage

Leite, C.; Silva, N.T.; Mendes, S.; Ribeiro, A.; De Faria, J.P.; Lourenço, T.; Santos, F.D.; et al, 2014. PLoS ONE. 10. 9. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84910047126&partnerID=MN8TOARS . 10.1371/journal.pone.0111059 . PLoS ONE

Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells

Ribeiro, A.; Laranjeira, P.; Mendes, S.; Velada, I.; Leite, C.; Andrade, P.; Santos, F.; et al, 2013. Stem Cell Research and Therapy. 5. 4. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84885350762&partnerID=MN8TOARS . 10.1186/scrt336 . Stem Cell Research and Therapy

A necrodane monoterpenoid from Lavandula luisieri essential oil as a cell-permeable inhibitor of BACE-1, the ß-secretase in Alzheimer's disease

Videira, R.; Castanheira, P.; Grãos, M.; Salgueiro, L.; Faro, C.; Cavaleiro, C., 2013. Flavour and Fragrance Journal. 380 - 388. 6. 28. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84885865286&partnerID=MN8TOARS . 10.1002/ffj.3156 . Flavour and Fragrance Journal

Inhibition of mitochondrial complex III blocks neuronal differentiation and maintains embryonic stem cell pluripotency

Pereira, S.L.; Grãos, M.; Rodrigues, A.S.; Anjo, S.I.; Carvalho, R.A.; Oliveira, P.J.; Arenas, E.; Ramalho-Santos, J., 2013. PLoS ONE. 12. 8. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84891590984&partnerID=MN8TOARS . 10.1371/journal.pone.0082095 . PLoS ONE

The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations

Ribeiro, C.A.; Fraga, J.S.; Grãos, M.; Neves, N.M.; Reis, R.L.; Gimble, J.M.; Sousa, N.; Salgado, A.J., 2012. Stem Cell Research and Therapy. 3. 3. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84861667226&partnerID=MN8TOARS . 10.1186/scrt109 . Stem Cell Research and Therapy

Excitotoxicity downregulates TrkB.FL signaling and upregulates the neuroprotective truncated TrkB receptors in cultured hippocampal and striatal neurons

Gomes, J.R.; Costa, J.T.; Melo, C.V.; Felizzi, F.; Monteiro, P.; Pinto, M.J.; Inácio, A.R.; et al, 2012. Journal of Neuroscience. 4610 - 4622. 13. 32. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84859013000&partnerID=MN8TOARS . 10.1523/JNEUROSCI.0374-12.2012 . Journal of Neuroscience

VEGF-functionalized dextran has longer intracellular bioactivity than VEGF in endothelial cells

Maia, J.; Vazão, H.; Pedroso, D.C.S.; Jesus, C.S.H.; Brito, R.M.M.; Grãos, M.; Gil, M.H.; Ferreira, L., 2012. Biomacromolecules. 2906 - 2916. 9. 13. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84866111153&partnerID=MN8TOARS . 10.1021/bm3009268 . Biomacromolecules

Towards the maturation and characterization of smooth muscle cells derived from human embryonic stem cells

Vazão, H.; das Neves, R.P.; Grãos, M.; Ferreira, L., 2011. PLoS ONE. 3. 6. 2011. http://www.scopus.com/inward/record.url?eid=2-s2.0-79952523704&partnerID=MN8TOARS . 10.1371/journal.pone.0017771 . PLoS ONE

Proteomics-based technologies in the discovery of biomarkers for multiple sclerosis in the cerebrospinal fluid.

Lourenço AS; Baldeiras I; Grãos M; Duarte CB; Lourenço, A.S.T.; Baldeiras, I.; Grãos, M.; Duarte, C.B., 2011. Current molecular medicine. 326 - 349. 4. 11. 2011. http://europepmc.org/abstract/med/21506919 . 10.2174/156652411795677981 . Current molecular medicine

Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells

Grãos, M.; Simões-Wüst, A.P.; Duarte, C.B.; Brenneisen, R.; Hamburger, M.; Mennet, M.; Ramos, M.H.; et al, 2010. Phytomedicine. 980 - 986. 12. 17. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-77956619629&partnerID=MN8TOARS . 10.1016/j.phymed.2010.03.005 . Phytomedicine

POLAR MAPPER: A computational tool for integrated visualization of protein interaction networks and mRNA expression data

Grãos, M.; Gonçalves, J.P.; Valente, A.X.C.N., 2009. Journal of the Royal Society Interface. 881 - 896. 39. 6. 2009. http://www.scopus.com/inward/record.url?eid=2-s2.0-69949092735&partnerID=MN8TOARS . 10.1098/rsif.2008.0407 . Journal of the Royal Society Interface

Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways

Almeida, R.D.; Manadas, B.J.; Melo, C.V.; Gomes, J.R.; Mendes, C.S.; Grãos, M.M.; Carvalho, R.F.; Carvalho, A.P.; Duarte, C.B., 2005. Cell Death and Differentiation. 1329 - 1343. 10. 12. 2005. http://www.scopus.com/inward/record.url?eid=2-s2.0-27144508812&partnerID=MN8TOARS . 10.1038/sj.cdd.4401662 . Cell Death and Differentiation

Growth-factor-dependent phosphorylation of Bim in mitosis

Grãos, M.; Almeida, A.D.; Chatterjee, S., 2005. Biochemical Journal. 185 - 194. 1. 388. 2005. http://www.scopus.com/inward/record.url?eid=2-s2.0-19544385223&partnerID=MN8TOARS . 10.1042/BJ20041385 . Biochemical Journal

Awards

2019

PhD studentship attributed to Heloísa Gerardo, Fundação para a Ciência e a Tecnologia

SFRH/BD/147316/2019

2017

PhD studentship attributed to Catarina Domingues, Fundação para a Ciência e a Tecnologia

SFRH/BD/115527/2016

2017

PhD studentship attributed to Tânia Lourenço, Fundação para a Ciência e a Tecnologia

SFRH/BD/114731/2016

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