@article{20289,
  abstract     = {Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally directed by self-generated signaling gradients rather than long-range, prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally and navigate through self-generated gradients remains largely unexplored. Here, we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that the relative chemotactic sensitivities of different cell populations control their long-time coupling and comigration dynamics, with boundary conditions such as external cell and attractant reservoirs substantially influencing the migration patterns. Our model predicts an optimal parameter regime that enables robust and colocalized migration. We test our theoretical predictions with in vitro experiments demonstrating the comigration of distinct immune cell populations, and quantitatively reproduce observed migration patterns under wild-type and perturbed conditions. Interestingly, immune cell comigration occurs close to the predicted optimal regime. Finally, we incorporate mechanical interactions into our framework, revealing a nontrivial interplay between chemotactic and mechanical nonreciprocity in driving collective migration. Together, our findings suggest that self-generated chemotaxis is a robust strategy for the navigation of mixed cell populations.},
  author       = {Ucar, Mehmet C and Zane, Alsberga and Alanko, Jonna H and Sixt, Michael K and Hannezo, Edouard B},
  issn         = {1091-6490},
  journal      = {Proceedings of the National Academy of Sciences},
  number       = {34},
  publisher    = {National Academy of Sciences},
  title        = {{Self-generated chemotaxis of mixed cell populations}},
  doi          = {10.1073/pnas.2504064122},
  volume       = {122},
  year         = {2025},
}

@article{15146,
  abstract     = {The extracellular matrix (ECM) serves as a scaffold for cells and plays an essential role in regulating numerous cellular processes, including cell migration and proliferation. Due to limitations in specimen preparation for conventional room-temperature electron microscopy, we lack structural knowledge on how ECM components are secreted, remodeled, and interact with surrounding cells. We have developed a 3D-ECM platform compatible with sample thinning by cryo-focused ion beam milling, the lift-out extraction procedure, and cryo-electron tomography. Our workflow implements cell-derived matrices (CDMs) grown on EM grids, resulting in a versatile tool closely mimicking ECM environments. This allows us to visualize ECM for the first time in its hydrated, native context. Our data reveal an intricate network of extracellular fibers, their positioning relative to matrix-secreting cells, and previously unresolved structural entities. Our workflow and results add to the structural atlas of the ECM, providing novel insights into its secretion and assembly.},
  author       = {Zens, Bettina and Fäßler, Florian and Hansen, Jesse and Hauschild, Robert and Datler, Julia and Hodirnau, Victor-Valentin and Zheden, Vanessa and Alanko, Jonna H and Sixt, Michael K and Schur, Florian KM},
  issn         = {1540-8140},
  journal      = {Journal of Cell Biology},
  number       = {6},
  publisher    = {Rockefeller University Press},
  title        = {{Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular matrix}},
  doi          = {10.1083/jcb.202309125},
  volume       = {223},
  year         = {2024},
}

@article{14274,
  abstract     = {Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.},
  author       = {Alanko, Jonna H and Ucar, Mehmet C and Canigova, Nikola and Stopp, Julian A and Schwarz, Jan and Merrin, Jack and Hannezo, Edouard B and Sixt, Michael K},
  issn         = {2470-9468},
  journal      = {Science Immunology},
  keywords     = {General Medicine, Immunology},
  number       = {87},
  publisher    = {American Association for the Advancement of Science},
  title        = {{CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration}},
  doi          = {10.1126/sciimmunol.adc9584},
  volume       = {8},
  year         = {2023},
}

@article{7420,
  abstract     = {β1-integrins mediate cell–matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic.},
  author       = {Sahgal, Pranshu and Alanko, Jonna H and Icha, Jaroslav and Paatero, Ilkka and Hamidi, Hellyeh and Arjonen, Antti and Pietilä, Mika and Rokka, Anne and Ivaska, Johanna},
  issn         = {1477-9137},
  journal      = {Journal of Cell Science},
  number       = {11},
  publisher    = {The Company of Biologists},
  title        = {{GGA2 and RAB13 promote activity-dependent β1-integrin recycling}},
  doi          = {10.1242/jcs.233387},
  volume       = {132},
  year         = {2019},
}

@article{5861,
  abstract     = {In zebrafish larvae, it is the cell type that determines how the cell responds to a chemokine signal.},
  author       = {Alanko, Jonna H and Sixt, Michael K},
  issn         = {2050-084X},
  journal      = {eLife},
  publisher    = {eLife Sciences Publications},
  title        = {{The cell sets the tone}},
  doi          = {10.7554/eLife.37888},
  volume       = {7},
  year         = {2018},
}