Related Experiment Video
Updated: May 7, 2026

Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Plasticity of primary microglia on micropatterned geometries and spontaneous long-distance migration in microfluidic
Susanna Amadio1, Adele De Ninno, Cinzia Montilli
1Santa Lucia Foundation/CNR-Cellular Biology and Neurobiology Institute, Via del Fosso di Fiorano 65, 00143 Rome, Italy. cinzia.volonte@cnr.it.
Background:
Microglia possess an elevated grade of plasticity, undergoing several structural changes based on their location and state of activation. The first step towards the comprehension of microglia's biology and functional responses to an extremely mutable extracellular milieu, consists in discriminating the morphological features acquired by cells maintained in vitro under diverse environmental conditions. Previous work described neither primary microglia grown on artificially patterned environments which impose physical cues and constraints, nor long distance migration of microglia in vitro. To this aim, the present work exploits artificial bio-mimetic microstructured substrates with pillar-shaped or line-grating geometries fabricated on poly(dimethylsiloxane) by soft lithography, in addition to microfluidic devices, and highlights some morphological/functional characteristics of microglia which were underestimated or unknown so far.
Results:
We report that primary microglia selectively adapt to diverse microstructured substrates modifying accordingly their morphological features and behavior. On micropatterned pillar-shaped geometries, microglia appear multipolar, extend several protrusions in all directions and form distinct pseudopodia. On both micropatterned line-grating geometries and microfluidic channels, microglia extend the cytoplasm from a roundish to a stretched, flattened morphology and assume a filopodia-bearing bipolar structure. Finally, we show that in the absence of any applied chemical gradient, primary microglia spontaneously moves through microfluidic channels for a distance of up to 500 μm in approximately 12 hours, with an average speed of 0.66 μm/min.
Conclusions:
We demonstrate an elevated grade of microglia plasticity in response to a mutable extracellular environment, thus making these cells an appealing population to be further exploited for lab on chip technologies. The development of microglia-based microstructured substrates opens the road to novel hybrid platforms for testing drugs for neuroinflammatory diseases.
Insights
Microglia exhibit remarkable plasticity, adapting their morphology and behavior to microstructured environments. These findings reveal novel insights into microglia migration and pave the way for new neuroinflammatory disease research platforms.
Area of Science:
- Neuroscience
- Cell Biology
- Biomaterials Science
Background:
- Microglia display significant plasticity, altering structure based on location and activation state.
- Understanding microglia's response to environmental cues is crucial for comprehending their function.
- Previous studies have not explored primary microglia on patterned substrates or their long-distance migration in vitro.
Purpose of the Study:
- To investigate the morphological and functional adaptations of primary microglia on artificial microstructured substrates.
- To explore microglia's behavior and migration in response to physical cues and constraints in vitro.
- To identify previously underestimated or unknown characteristics of microglia.
Main Methods:
- Fabrication of bio-mimetic microstructured substrates (pillar-shaped and line-grating geometries) using soft lithography.
- Utilizing microfluidic devices to control and observe microglia behavior.
- Culturing primary microglia on these engineered environments to assess morphological and migratory responses.
Main Results:
- Primary microglia adapt their morphology and behavior to diverse microstructured substrates.
- On pillar-shaped geometries, microglia become multipolar with extensive protrusions.
- On line-grating geometries and microfluidic channels, microglia adopt a stretched, bipolar morphology with filopodia.
- Microglia spontaneously migrate up to 500 μm in microfluidic channels over 12 hours (avg. speed 0.66 μm/min) without chemical gradients.
Conclusions:
- Microglia demonstrate high plasticity in response to mutable extracellular environments.
- These findings support the exploitation of microglia in lab-on-a-chip technologies.
- Development of microglia-based microstructured substrates offers novel platforms for testing drugs for neuroinflammatory diseases.

