Team:MIT/Description

Project Inspiration and Description

Inspiration

Swarm behavior is defined as a large group of individuals performing a collective function, usually movement, without each member directly being aware of the overall goal. In particular, only a few members of the group determine the swarm’s motion: these are known as leaders. In nature, these patterns can be seen in the flight patterns of birds and insects. In such animal hierarchies, the alphas lead from the front while the rest know to stay in the group and follow those before them. These basic individual interactions allow for more complex dynamics when operated by a controlling subgroup.

The Wyss Institute at Harvard University was able to recreate such swarm behaviors using robots. They programmed thousands of small robots with simple movement patterns that were facilitated by sensors on each robot to detect proximity to other units. A few seed robots were specifically placed and programmed such that they could influence the movement of the follower units into a specifically shaped formation. Equipped with sensors to detect proximity to other units, the follower robots could move around each other in an orderly fashion until the final shape was achieved. In summary, a crowd of units is able to work towards and accomplish the same objective despite that target function only being encoded in a few of the units. Looking at these natural and robotic swarms, we were inspired to create biological cell swarms. In biology, swarm behavior already exists at the microscopic level among cells through chemotaxis. Chemotaxis is the directed movement of cells up or down a chemical gradient. The chemical stimulus, known as a chemokine, is secreted by certain cells and cause other cells to polarize toward or away from the chemokine source. The chemokine is usually a ligand for an actin polymerization pathway. Chemotaxis plays a critical role in a variety of biological systems such as immune response, cancer metastasis, and the development of multicellular organisms.

The swarming nature of certain white blood cells in the natural adaptive immune response is currently the most widely used model for chemotaxis. Neutrophils (the body’s largest group of white blood cells) primarily fight infections and repair damaged tissues as a party of the natural adaptive immune response. When dealing with infections, neutrophils detect certain chemicals released by pathogens so they can follow, surround, and destroy them. Cells in damaged tissues can release chemokines to attract neutrophils to the area to stimulate the repair process. Both of these chemotactic behaviors result in swarms of neutrophils to a target site in the body. We wondered if we could harness this behavior in a more controlled manner in our project.

Description

Cell coordination depends on the ability of cells to accurately receive and respond to stimuli from both the environment and other cells. Chemotaxis, is one such form of cell coordination that is essential for many biological processes. The ability to harness this chemotactic power within a single cell would allow for more controlled swarming behavior that we could employ towards various applications.

Our goal was to control chemotactic behavior in neutrophils by engineering HEK cells to secrete chemokines. By secreting chemokines, the HEK cells would become ‘leaders’ while the neutrophils that respond and move towards them would become ‘followers’. As a result, the basis for cell swarming could be established.

For our project, we chose to work with HL-60 progenitor cells, which we cultured and differentiated into neutrophil-like cells. First, we tested neutrophil chemotaxis towards different endogenous chemoattractants as a control experiment. Next, we transfected our leader HEK cells with chemokine genes (namely Interleukin-8 or IL-8), and verified transfection success using assays to test for and quantify chemokine secretion. Finally, we used migration assays and microscopy to assess neutrophil chemotaxis towards the secreted chemokines alone (isolated from the transfected HEK cells), and towards intact leader HEK cells that directly secreted the chemokines into the cellular environment.