Tracking cell migration in three dimensions

The ability of cells to move and migrate is important for many biological processes.

Cells migrate to other parts of the body during tumor metastasis and mobilize to attack foreign invaders when mounting an immune response. Imaris software is helping scientists to understand the biological mechanisms involved in cell migration by providing detailed visualization and precise tracking of cells in three dimensions. This knowledge could be used to develop new treatments for diseases linked with cell migration.

Cancer cell invasion

Since cells don’t operate alone, they are best studied in an environment where they interact with other cells and tissues during migration. Researchers have developed various types of biological systems to study cells in an environment mimicking that of a living organism. For example, Nicholas Kurniawan from the FOM Institute AMOLF in Amsterdam and researchers from the National University of Singapore developed a collagen hydrogel model with adjustable mechanical properties to study the three-dimensional invasion of highly malignant breast cancer cells.

The researchers used the Imaris tracking algorithm to follow cells in the presence and absence of drugs that affect four typical mechanisms of cell migration in five different extracellular matrices with varying biophysical properties. Without drug treatment, cancer cell motility showed a weak dependence on matrix mechanics. After adding anti-migratory drugs, the researchers found that drug effectiveness depended on the biophysical conditions of the three-dimensional matrix. These findings offer concrete guidelines for selecting the most effective pharmacological approaches for different biophysical conditions of the tumor.

Immune response to neuroinflammation

Researchers are also are studying 3D cell migration to better understand the role of inflammation in neurodegenerative disease such as Alzheimer’s and Parkinson’s disease. A group led by Dr. Stephen F. Traynelis from Emory University School of Medicine, in collaboration with a team led by Katerina Akassoglou at the Gladstone Institute, used Imaris to track microglial responses to neuroinflammation in three dimensions.

To observe how microglia respond to tissue damage and cell death, the researchers acquired in vivo two-photon and confocal images of microglia in lipopolysaccharide (LPS)-treated mice, a model of peripherally induced neuroinflammation. Using 3D reconstructions created with Imaris, they examined the complex morphology of microglia and also tracked these highly motile cells over time. The experiments revealed that in the absence of tissue damage, microglia in LPS-injected mice were highly motile. However after experimentally induced inflammation, the microglia displayed slower motility in response to damage. These findings show that inflammation can change the morphology and motility of microglia. Microglia that are activated by neuroinflammation may be inefficient in responding to and clearing the damage, which could ultimately impair the function of surrounding neurons in a way that leads to disease.

Neuroinflammation and multiple sclerosis

Imaris software is helping Dr. Joel S. Pachter, Debayon Paul and colleagues from the Blood-Brain Barrier Laboratory at the University of Connecticut Health Center learn more about the neuroinflammatory processes that occur in diseases such as multiple sclerosis (MS). The characteristic nerve damage of MS is caused by an autoimmune response that damages the myelin sheaths of nerve cells. A central nervous systems (CNS) signaling protein called chemokine CCL2 plays a critical role in this process by guiding white blood cells, or leukocytes, across the blood-brain barrier.

The researchers used an animal model of MS to identify the CCL2 sources that contribute to leukocyte migration in neuroinflammatory disease and to discover the mechanism(s) involved in this migration. As part of the study they used the Imaris spot creation wizard to study the behavior of leukocytes in 3D. The Imaris Vantage plot module let them graphically display different 3D profiles of spot objects representing the spatial location of separate luminal and perivascular leukocytes associated with inflamed CNS microvessels. Their data demonstrated that CNS astrocyte and endothelial pools of CCL2 each regulate different stages of neuroinflammation in this mouse model. Targeting drugs to these sources could more effectively mitigate neuroinflammatory disease.

Easy analysis of 3D data

When studying 3D cell migration, scientists typically need quantitative data that describes motility behaviors. Imaris provides a variety of measurements to facilitate this analysis. Using both table and graph formats, the software displays data on how a cell’s size, shape and fluorescence intensity changes over time. It can also automatically calculate statistical values for migration duration, length and straightness as well as displacement. Available speed information includes velocity, average speed and speed variability.

From version 8.2 (December 2015) Imaris included some new features that are particularly helpful for 3D cell migration and lineage tracking analysis. It improved the workflow required to visualize and analyze long 3D time-lapse datasets by offering faster conversion from the native to IMS file, which translates into less time needed to open and visualize large datasets.

Bitplane continues to bring innovative features to its software to help scientists more easily work with large datasets and to get even more detailed 3D information about cell migration. These advances are helping scientists to better understand why and how cells move and the signaling involved in 3D cell migration.

Read more about the featured research:

Tracking cancer cell invasion in 3D matrices

Studying 3D location and behavior of cells during neuroinflammatory processes

3D tracking of microglial response to neuroinflammation