Publications by authors named "Kolade Adebowale"

Macrophages and T cells communicate under homeostatic and pathological conditions. Previous studies elucidated biochemical crosstalk between macrophages and T cells. However, recent technological advances in multiplex tissue imaging reveal that these cells are often located proximally.

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Circulating monocytes are recruited to the tumor microenvironment, where they can differentiate into macrophages that mediate tumor progression. To reach the tumor microenvironment, monocytes must first extravasate and migrate through the type-1 collagen rich stromal matrix. The viscoelastic stromal matrix around tumors not only stiffens relative to normal stromal matrix, but often exhibits enhanced viscous characteristics, as indicated by a higher loss tangent or faster stress relaxation rate.

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Cell migration is pivotal in cancer metastasis, where cells navigate the extracellular matrix (ECM) and invade distant tissues. While the ECM is viscoelastic-exhibiting time-dependent stress relaxation-its influence on cell migration remains poorly understood. Here, we employ an integrated experimental and modeling approach to investigate filopodial cancer cell migration on viscoelastic substrates and uncover a striking transition from sub-diffusive to super-diffusive behavior driven by the substrate's viscous relaxation timescale.

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Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non-injectable, to clinical studies. In an article published in 2020 entitled "Hydrogels in the clinic", we reviewed the clinical landscape and translational challenges of injectable hydrogels.

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Cellular hitchhiking is an emerging strategy for the control of adoptively transferred immune cells. Hitchhiking approaches are primarily mediated by adhesion of nano and microparticles to the cell membrane, which conveys an ability to modulate transferred cells local drug delivery. Although T cell therapies employing this strategy have progressed into the clinic, phagocytic cells including dendritic cells (DCs) are much more challenging to engineer.

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Article Synopsis
  • Type 2 diabetes is linked to an increased risk of hepatocellular carcinoma (HCC), with advanced glycation end-products (AGEs) playing a critical role in this connection.
  • The study shows that AGEs change collagen structure and increase the viscoelasticity of the extracellular matrix (ECM) without affecting its stiffness, promoting HCC growth in both patients and animal models.
  • High levels of viscoelasticity, driven by AGEs, facilitate HCC cell proliferation and invasion through a specific mechanotransductive pathway, suggesting a new target for therapeutic intervention.
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Traumatic brain injury (TBI) is a debilitating disease with no current therapies outside of acute clinical management. While acute, controlled inflammation is important for debris clearance and regeneration after injury, chronic, rampant inflammation plays a significant adverse role in the pathophysiology of secondary brain injury. Immune cell therapies hold unique therapeutic potential for inflammation modulation, due to their active sensing and migration abilities.

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  • Circulating monocytes can differentiate into macrophages in tumors and need to migrate through a dense collagen-rich environment to do so.
  • Research shows that increased stiffness and faster stress relaxation of the surrounding matrix enhance monocyte migration.
  • Monocyte migration relies on actin polymerization at the leading edge rather than matrix adhesions, allowing them to create paths through the viscous matrices.
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Cell therapies are emerging as a promising new therapeutic modality in medicine, generating effective treatments for previously incurable diseases. Clinical success of cell therapies has energized the field of cellular engineering, spurring further exploration of novel approaches to improve their therapeutic performance. Engineering of cell surfaces using natural and synthetic materials has emerged as a valuable tool in this endeavor.

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  • Most extracellular matrices (ECMs) display dissipative behaviors, which significantly affect how cancer cells move and invade through tissues.
  • This study introduces a chemo-mechanical model that analyzes the growth of invadopodia—protrusions used by cancer cells—taking into account various biological processes and how they interact with the mechanical properties of the surrounding ECM.
  • The findings emphasize the importance of matrix plasticity in influencing invadopodia dynamics, potentially guiding the creation of biomaterials that can control cancer cell movement.
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Cell migration on two-dimensional substrates is typically characterized by lamellipodia at the leading edge, mature focal adhesions and spread morphologies. These observations result from adherent cell migration studies on stiff, elastic substrates, because most cells do not migrate on soft, elastic substrates. However, many biological tissues are soft and viscoelastic, exhibiting stress relaxation over time in response to a deformation.

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Cancer cells typically invade through basement membranes (BMs) at key points during metastasis, including primary tumor invasion, intravasation, and extravasation. Cells extend invadopodia protrusions to create channels in the nanoporous BM through which they can invade, either via proteolytic degradation or mechanical force. Increased matrix stiffness can promote cancer progression, and two-dimensional (2D) culture studies indicate that increased stiffness promotes invadopodia degradation activity.

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Studies of cancer cell migration have found two modes: one that is protease-independent, requiring micron-sized pores or channels for cells to squeeze through, and one that is protease-dependent, relevant for confining nanoporous matrices such as basement membranes (BMs). However, many extracellular matrices exhibit viscoelasticity and mechanical plasticity, irreversibly deforming in response to force, so that pore size may be malleable. Here we report the impact of matrix plasticity on migration.

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