The Great Escape:
How Cells Migrate to Shape Life and Disease

ibidi Blog | April 3, 2025 | Abhishek Derle, ibidi GmbH

Imagine you injure your knee. Almost instantly, your body springs into action. Skin cells migrate to close the wound, immune cells rush in to fight infection, and blood vessels reorganize to restore circulation. From the earliest stages of embryonic development to the regeneration of damaged tissues, cell migration is a fundamental process that shapes life itself.

Cells don’t move randomly—they follow precise signals, navigating through tissues with remarkable accuracy. This ability to migrate underlies critical biological functions, including organ formation, wound healing and defense against infections. However, when these tightly regulated mechanisms become disrupted, they can contribute to diseases such as chronic inflammation, autoimmune disorders, and even cancer [1].

So how do cells know where to go? How do they move? And how can scientists study and manipulate these mechanisms to better understand health and disease? Let’s dive into the fascinating world of cellular migration.

How and Why Do Cells Move?

Cells may not walk, but they do have a complex internal skeleton that allows them to extend and contract, propelling themselves through tissues. Their movement is not random—it is highly coordinated and regulated by external signals and internal signaling cascades. Broadly speaking, cells migrate using different mechanisms [2]:

• Amoeboid Migration: Cells push forward by extending protrusions (like pseudopodia) and squeezing through gaps, much like how an amoeba moves.
• Mesenchymal Migration: Cells adhere to surrounding structures and pull themselves forward using actin-rich protrusions called lamellipodia and filopodia.
• Collective Migration: Groups of cells move together as a coordinated unit, essential in processes like wound healing and embryonic development.

Diversity in cell migration strategies

Cell Migration in Development and Healing

From the earliest stages of life, cells are on the move. In the developing embryo, neural crest cells migrate over long distances to form structures like the heart, bones, and nervous system. Without precise migration, birth defects and developmental disorders can occur. This highly coordinated process ensures that organs and tissues develop in the right place at the right time, shaping the body’s structure and function [3].

Later in life, cell migration plays a central role in wound healing and tissue regeneration. When tissue is damaged, keratinocytes, fibroblasts, and immune cells work together to repair the injury. Fibroblasts migrate into the wound, depositing collagen to form new tissue, while endothelial cells create new blood vessels through angiogenesis, restoring oxygen and nutrient supply [4]. Immune cells, guided by chemotaxis, rush to the injury site to fight infection, clear debris, and modulate inflammation [5]. This intricate cellular coordination ensures efficient healing and prevents chronic wounds or excessive scarring.

By studying cell migration in development and healing, scientists can better understand how cells navigate their surroundings, respond to signals, and coordinate their movements. Live-cell imaging allow researchers to watch these tiny travelers in action, capturing how cells push, pull, and collaborate to build tissues and repair damage. These insights reveal not only the beauty of organized migration but also what happens when this control is lost. While precise migration is essential for building organs and healing wounds, the ability of cells to move can also take a dark turn—fueling diseases like cancer, where rogue cells break free and invade new territories.

The Dark Side: Cancer Metastasis and Uncontrolled Migration

While controlled migration is essential for life, the ability of cells to move can also drive deadly diseases. One of the most feared aspects of cancer is metastasis, the process where tumor cells break away, travel through the bloodstream or lymphatic system, and establish secondary tumors in distant organs [6]. Cancer cells exploit many of the same mechanisms used by normal cells but with a dangerous twist:

• They often undergo epithelial-to-mesenchymal transition (EMT), which allows them to detach from the primary tumor and become more mobile.
• Once mobile, the cells ignore the usual stop signals and push through tissue barriers.
• To facilitate their journey, the cancer cells hijack angiogenesis—the process of forming new blood vessels. These new vessels provide a direct route for the cancer cells to migrate through the body, offering them access to distant organs where they can establish secondary tumors and drive further disease progression.

Uncontrolled migration in cancer metastasis [7]

Cell Migration and Disease Beyond Cancer

While cancer metastasis is the most infamous example of uncontrolled migration, aberrant cell movement is also implicated in other diseases:

• Inflammatory Diseases: In conditions like rheumatoid arthritis and asthma, immune cells migrate excessively, leading to chronic inflammation and tissue damage.
• Neurodegenerative Disorders: Abnormal migration of neurons during development is linked to disorders like epilepsy and schizophrenia [8].
• Fibrosis: When fibroblasts migrate too aggressively, excessive scar tissue forms in organs like the lungs (pulmonary fibrosis) or liver (cirrhosis), impairing function [9].

How Scientists Study Cell Migration

Studying cell migration is essential for understanding key biological processes, including tissue repair, immune response, and cancer metastasis. However, traditional migration assays often face challenges in reproducibility, physiological relevance, and real-time observation. Researchers are continuously refining methods to overcome these limitations and gain deeper insights into cellular movement.

Wound Healing Assays

A wound healing assay is used to study how cells migrate to close a gap, mimicking tissue repair processes in the body. This technique is widely applied in research on regeneration, fibrosis, and tumor cell migration. However, inconsistencies in wound size and shape can lead to variable results, and mechanical scratching may affect cell behavior. Using defined cell-free gaps instead of manual scratches helps ensure more reproducible and quantifiable wound healing experiments.

ibidi solution: In contrast to the traditional scratch assay, the ibidi Culture-Inserts create a precise, cell- and debris-free gap. This enables excellent reproducibility and accurate comparison of different wound healing and cell migration experiments.

ibidi Culture-Inserts

Scratch assay

Chemotaxis Assays

A chemotaxis assay examines how cells move in response to chemical gradients, playing a vital role in immune response, embryonic development, and cancer metastasis. Traditional Boyden chambers lack real-time visualization, limiting analysis to endpoint measurements and providing limited insights into migration patterns.

The ibidi µ-Slide Chemotaxis offers real-time chemotaxis measurement in both 2D and 3D environments, enabling detailed observation of cell movement under controlled gradients. This allows researchers to track migration dynamics continuously, providing more accurate and quantitative analysis of directional movement and cellular behavior

Sprouting and Invasion Assays

Sprouting and invasion assays are used to study how cells invade surrounding tissues, an essential process in angiogenesis, cancer metastasis, and tissue remodeling. In sprouting assays, endothelial cells form new capillary-like structures, mimicking blood vessel formation. In invasion assays, cancer or stromal cells migrate into 3D matrices, replicating tumor infiltration. Traditional methods often rely on complex co-culture systems or artificial scaffolds that may not fully replicate physiological conditions.

ibidi solution: The ibidi µ-Slide Angiogenesis and the micro-Insert 3D provide controlled environments for studying cell sprouting and invasion under defined conditions. These systems enable high-resolution imaging, allowing researchers to analyze the dynamics of vascularization and tumor cell invasion in more physiologically relevant settings.

Transwell Migration Assays

A transwell migration assay is commonly used to study how cells move through porous membranes, simulating tissue barriers such as the blood-brain barrier or endothelial layers. It is frequently applied in cancer research, immunology, and drug testing. While conventional transwell assays are effective for studying cell migration, they may not fully replicate the complexity of native in vivo conditions, as they typically use artificial membranes that do not completely mimic the extracellular matrix or tissue architecture. Additionally, these assays can limit microscopy access and visualization, hindering real-time observation of cell behavior.

ibidi solution: The ibidi micro-Insert 3D provides a more relevant and accessible alternative, offering a natural 3D environment without the use of artificial membranes, allowing for superior microscopy access and accurate observation of cell invasion and migration in conditions closer to native tissue.

micro-Insert 3D
Mimics native in vivo conditions combined with excellent microscopy access

Transwell Inserts
Often fail to fully mimic native in vivo conditions, incompatible with real time imaging

Microfluidic Assays

Microfluidic systems allow researchers to study how fluid flow and shear stress influence cell migration—factors that play a crucial role in vascular biology, metastasis, and tissue engineering. Traditional static culture conditions do not replicate these dynamic environments, limiting the physiological relevance of migration studies. Experimental setups that integrate controlled flow conditions help researchers analyze how shear stress and interstitial flow impact cell movement and adhesion.

ibidi solution: The µ-Slide I Luer 3D , combined with the ibidi Pump System,  enables controlled studies of transmigration. With endothelial cells on the luminal side and cancer cells on the basal side, it mimics in vivo conditions, allowing shear stress application for realistic flow studies.

Conclusion: The Future of Cell Migration Research

Cell migration is one of the most fundamental yet complex processes in biology. It dictates how we develop, how we heal, and—when it goes wrong—how diseases progress. By studying this intricate dance, researchers can unlock new treatments for everything from wound healing to cancer therapy.

With cutting-edge tools like advanced live cell imaging, micropatterned environments [10] and microfluidic systems scientists can now observe and manipulate cell migration with unprecedented precision. These technologies are paving the way for discoveries that may one day help us stop cancer in its tracks, accelerate tissue regeneration, and better understand the mysteries of life at the cellular level.

As we continue to explore the great escape of cells, one thing is clear: understanding migration isn’t just about watching cells move—it’s about uncovering the secrets of life itself.

References

1. Pourjafar, M. and V.K. Tiwari, Plasticity in cell migration modes across development, physiology, and disease. Frontiers in Cell and Developmental Biology, 2024. 12.
2. Kunwar, P.S., D.E. Siekhaus, and R. Lehmann, In vivo migration: a germ cell perspective. Annu Rev Cell Dev Biol, 2006. 22: p. 237-65.
3. Kurosaka, S. and A. Kashina, Cell biology of embryonic migration. Birth Defects Res C Embryo Today, 2008. 84(2): p. 102-22.
4. Mayya, C., et al., Mechanisms of Collective Cell Migration in Wound Healing: Physiology and Disease, in Wound Healing Research: Current Trends and Future Directions, P. Kumar and V. Kothari, Editors. 2021, Springer Singapore: Singapore. p. 55-74.
5. Delgado, M.G. and A.-M. Lennon-Duménil, How cell migration helps immune sentinels. Frontiers in Cell and Developmental Biology, 2022. 10.
6. Aceto, N., et al., Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell, 2014. 158(5): p. 1110-1122.
7. Reisenauer, K., The Other EMT: Exploring the controversial driver of metastasis, Z. Tang, Editor. 2019: Oncobites,The Latest in Cancer Research, simplified.
8. Esteve, D., et al., Adult Neural Stem Cell Migration Is Impaired in a Mouse Model of Alzheimer's Disease. Mol Neurobiol, 2022. 59(2): p. 1168-1182.
9. González, D., et al., Role of WISP1 in Stellate Cell Migration and Liver Fibrosis. Cells, 2024. 13(19).
10. Li, Y., et al., Advances in Regulating Cellular Behavior Using Micropatterns. Yale J Biol Med, 2023. 96(4): p. 527-547.