Nanoparticles to Study Osteocytes

To understand how bone is built and how it degrades with age or disease, we need to understand the functioning of the cells within bone. Osteocytes are cells embedded within bone and are critical for maintaining healthy bone tissue. There are a huge number of osteocytes in your bones (around 42 billion in an adult human!) and they form an intricate network of connections in their environment to sense and respond to signals from the body. If you picture a 3D maze built into concrete with a cell at each branching path, that is almost how osteocytes are organized within bone. They don’t move much, but can communicate through long dendrites that extend from the main body of the cell and form connections with other cells.

The unique and labyrinthine environment of osteocytes within bone makes them very difficult to study. Most research has been done on slices of bone or on cells that have been removed from bone and put on a dish. However, cells act very differently when removed from their natural environment, and looking at cells after they have been taken out of the body loses a lot of information about the dynamic activity of the cells, like how they act over time.

Our lab wants to study these cells in their natural environment and to understand how they function in a living animal. To see through the concrete of bone to the cells, we use multiphoton microscopy and fluorescent nanoparticles.

An injection of bright nanoparticles allows osteocytes to be visualized inside of bone in their natural environment.

The channels between cells in bone are tiny, only very small particles can travel through them and interact with the cells, showing us where they are and what they are doing. Most ways that scientists light up target cells uses proteins or particles that are too large to fit through the channels in bone. It would be like trying to fit a beach ball down a shower drain. So we use nanoparticles that emit a very bright light and are small enough to travel through bone to osteocytes. They have a diameter of about 7 nanometers, which means you could fit around 100,000 of the particles in the period at the end of this sentence. We inject these nanoparticles under the skin, and very quickly they move through bone and are taken up by osteocytes. These nanoparticles are much smaller than the cells: think about putting a pencil eraser into a full size school bus, but with enough of them, they make the cells appear bright under our microscope!

Our nanoparticles can be made with different colors and can target different parts of the cell, allowing us to ask many questions about cell activity in their natural environment. Even better, these particles are so small that they can be used over time and don’t have a negative impact on the cells!

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Microscopy in Bone