Abdel Rahman Abdel Fattah 

Multiscale mechanobiology of tissue organization

Our Research Focus

Our group combines local active mechanical stimulation with readouts of cell-driven extracellular matrix (ECM) dynamics, using bioengineered stimulation tools, time-lapse microscopy, particle image velocimetry (PIV), image analysis, and simulations. Combined with longitudinal observations (using reporter cell lines) of morphological, cytoskeletal, tissue tension and cell fate changes, we aim to gain a dynamic understanding of how local forces lead to emergent features and properties that affect the cellular and extracellular neighborhoods at the multicellular level.

Key Research Areas

• Dynamic Cellular and ECM Interactions: By integrating longitudinal observations of morphological, cytoskeletal, tissue tension, and cell fate changes using reporter cell lines, we investigate how local forces drive changes at the multicellular level.
• Metabolomics: Our goal is to gain a fundamental understanding of the energy landscape required to achieve or maintain organized states of low entropy.
• Spatial Transcriptomics and Atomic Force Microscopy: Ultimately, we will use spatial transcriptomics to profile the molecular landscape in combination with atomic force microscopy to obtain mechano-transcriptomic maps. This will not only bridge scales (multicellular to molecular) but also fields (molecular to mechanical) revealing molecular response signatures to changes in mechanics and unraveling drivers of tissue organization.
• Functional Validation: Using genetic engineering and pharmacological inhibitors, we will functionally the identified drivers of tissue organization.

Disease Models

Our disease models are centered around trauma and how excessive forces cause tissue disorganization. We focus particularly on the role of ECM dynamics in posttraumatic injury progression in brain organoid models, with the aim of identifying targets that may limit, stop, or reverse neuronal loss. We also have a focus on liver diseases, particularly fibrosis, and how local ECM variations mediate injury in hepatocyte neighborhoods. 

Comprehensive Models of Tissue Organization

Advances in computational fields can leap the mechanobiology field forward through multimodal data integration, combining multicellular, cellular, molecular, and mechanical data into one comprehensive space. We will use machine learning  techniques to integrate and extract important features that drive organization phenotypes. In addition, we will build mathematical formulations based on reaction-diffusion and positional information models that attempt to explore the physical laws that spatiotemporally govern tissue organization. Altogether, we aspire to understand tissue organization from a mechanical standpoint by building a data-rich navigation map of organization phenotypes and paths. This map will help us predict not just how organization is maintained, but also where (along an organization path) and how (molecular, cellular and mechanical players involved) organization may ‘go wrong’ at the onset of disease (particularly neuronal loss or degeneration). 

Biosketch

Abdel Rahman Abdel Fattah studied Mechanical Engineering at McMaster University (Canada). He gained industry experience in the renewable energy industry in Ontario before returning to McMaster University to complete his PhD. There, he combined magnetic and fluid dynamics theories to manipulate synthetic and biological materials and fabricate mechanically anisotropic polymers, print carbon-nanotube biosensors, and bioprint 3D cellular constructs for tissue engineering applications. For his postdoctoral studies, Abdel chose Europe to dive into the world of mechanobiology in the Lab of Morphogenesis and Bioengineering at KU Leuven (Belgium) under the mentorship of Professor Adrian Ranga. There he focused on the mechanoregulation of neural tube development. He developed a hydrogel-embedded human neural tube organoid model and a single-cell transcriptomic atlas for stretched organoids, revealing key mechanical-stress molecular-responders involved in enhancing floorplate patterning. He advanced mechanical stimulation approaches by developing a high throughput local stimulation method through magnetic microactuators embedded within organoids. This revealed that force location acts as a frame of reference for symmetry breaking and multicellular patterning in organoids. Continuing to investigate cell-fate dynamics, Abdel also developed an in-silico positional information model showing that floorplate patterning may be predetermined from the position of randomly emerging cells of the same fate. He went on to investigate the relationship between epithelial morphogenesis, symmetry-breaking events and extracellular matrix (ECM) dynamics. This work revealed a reciprocal relation between ECM flow and morphological events that define the transcriptomic landscape in pre-streak-like epithelia. Abdel joined CeMM in September 2022 as a Postdoc in the Lab of Giulio Superti-Furga where he focused on the metabolic dimension of fate mechanoregulation. Now, as a Principal Investigator at CeMM (since August 2024) his lab focuses on understanding how cells navigate a mechanical roadmap in order to initiate, achieve, and maintain tissue organization in health and disease. His lab will lead this research direction by building new bioengineering tools, profiling transcriptomic landscapes, and bridging the multicellular and molecular dimensions of mechanoregulation.

Selected Papers

A R. Abdel Fattah, S. Grebenyuk, L. P. M. H. de Rooij, I. Salmon, A. Ranga, Neuroepithelial organoid patterning is mediated by a neighborhood watch mechanism, Cell Reports 2023. (abstract) (abstract)

A R. Abdel Fattah (co-corresponding author), N. Kolaitis, K. Van Daele, B. Daza, G. Rustandi, A. Ranga, Targeted mechanical stimulation via magnetic nanoparticles guides in vitro tissue development, Nature Communications, 2023. (abstract)

S. Grebenyuk, A R. Abdel Fattah,  G. Rustandi, M. Kumar, B. Toprakhisar, I. Salmon, C. Verfaillie, A. Ranga, Engineering large-scale perfused tissues via synthetic 3D soft microfluidics, Nature Communications, 2023. (abstract) 

I. Salmon, S. Grebenyuk, A R. Abdel Fattah, G. Rustandi, T. Pilkington, C. Verfaillie, A. Ranga, Engineering neurovascular organoids with 3D printed microfluidic chips, Lab on a Chip, 2022. (abstract) 

A R. Abdel Fattah, B. Daza, G. Rustandi, M. A. Berrocal-Rubio, B. Gorissen, S. Poovathingal, K. Davie, J. Barrasa-Fano, M. Cóndor, X. Cao, D. H. Rosenzweig, Y. Lei, R. Finnell, C. Verfaillie, M. Sampaolesi, P. Dedecker, H. Van Oosterwyck, S. Aerts, A. Ranga, Actuation Enhances Patterning in Human Neural Tube Organoids, Nature Communications, 2021. (abstract)

S. Mishriki, A R. Abdel Fattah (co-first author),  T. Kammann, R. P. Sahu, F. Geng, I. K. Puri, Rapid Magnetic 3D Printing of Cellular Structures with MCF-7 Cell Inks, Research, 2019. (abstract) 

A R. Abdel Fattah, S. Mishriki, T. Kammann, R. P. Sahu, F. Geng, I. K. Puri, Gadopentatic Acid Affects in vitro Proliferation and Doxorubicin Response in Human Breast Adenocarcinoma Cells, Biometals, 2018, 31, p. 605-616. (abstract)

A R. Abdel Fattah, S. Mishriki, T. Kammann, R. P. Sahu, F. Geng, I. K. Puri, 3D Cellular Structures and Co-Cultures Formed through Contactless Magnetic Manipulation of Cells on Adherent Surfaces, RSC Biomaterial Science, 2018, 6, p. 683-694. (abstract)

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