important, you’re just having a friendly chat about your day at work, catching them

up on some office gossip. While you’re texting, you check social media and see that the friend

you’re texting with posted a video of their new baby and it’s adorable so you send them

a message through that social media app. Now you’re in a pickle. For us overthinkers,

this is a nightmare. Do you acknowledge that you’re having two separate conversations

through two different apps? Do you keep on living this double life where two different

realities of yourself exist in a kind of Shrodingers text message situation? Do you do the unthinkable

and call that person on the phone?! This is what our cells are trying to juggle at a much

bigger level, but without the added pressure of social contracts. You don’t just have

two different conversations happening in two different apps, you have trillions of conversations

happening between cells or within cells. Both between cells right next to each other and

between cells over a meter apart. And it’s not just the number of messages, but the mode

of messaging. So in today’s video, we’re going to learn what exactly is a cellular

message and how cells get messages from point A to point B. Because I hate to break it

to you, but cells don’t use emoji.

In order to communicate, you have to have some kind

of language. And while I’ve personally had conversations in a language composed entirely

of Nicholas Cage gifs, your cells aren’t quite as sophisticated. I know what you’re

thinking, that is clearly a man of exquisite taste and culture and I agree. Your cells

on the other hand speak a language of chemicals. The message they send out is a chemical called

a ligand. These ligands come in all shapes and sizes — calling something a ligand just

means it’s a molecule that binds to a receptor. And receptors are exactly what they sound like,

some kind of protein built to receive a particular ligand. These things can be on the outside

of the cell or within a cell, and as you can imagine, there’s a time and place to use

different ligands and receptors. Like we mentioned in our hormone episode, some chemicals

like steroids can cross the cell membrane and bind to receptors inside the cell. But

other protein-based hormones can’t pass through the membrane, but they can bind to

receptors on the surface of the cell, and communicate their message that way. Once

the ligand binds to a receptor, the chemical message gets interpreted and any number of

biological reactions can happen — cellular processes can start or speed up or slow down,

often leading to complex chains of events that make up the important processes in our

biology. But in this video we’re focusing on how messages are spoken and heard, not

what the cells do with that information. Right off the bat, when we’re looking at the different

ways cells communicate, we care about the distance that the ligand has to travel. Just

like when you communicate with your friends, some modes of communication are built for

different situations. In some cases, cells can be in direct contact and pass ligands

straight to each other. It’s especially useful when you want to pass tiny particles

like Calcium and other ions through to neighboring cells. In this case, Calcium is the ligand

that’s sent off to a receptor in the neighboring cell. Not surprisingly, this method is called

direct signaling, and we can see it in action in the electrical activity of the heart muscle.

As a general rule, you want your heart muscle to contract in sync with other parts of the

heart muscle, and to do that, your heart needs to transmit an electrical signal across itself

extremely quickly. So the heart has little proteins between each cardiac muscle called

gap junctions that let ions pass through super fast. It’s basically a direct connection

from the inside of one cell to another that’s only big enough for very tiny particles. This

makes for a faster and more coordinated contraction, ultimately allowing for a normal heart beat.

But eventually our cells have to start talking with other types of cells, which is what the

next type of direct signaling does well. Almost all of our cells have proteins on their surfaces,

and other cells can have complementary matching proteins on their surfaces, like a lock and

key. When those proteins match up to proteins on other cells, they create some kind of reaction

and pass on the signal. Think about it like passing notes in class. You could write a

note, crumple it up, and kick it across the ground to your friend, or you could just hand

it off. This is a fool-proof note passing strategy, trust me, I was a junior high teacher. This

type of cell communication is how our immune systems distinguish healthy cells from foreign

invaders. Our healthy cells have a protein on its surface called major histocompatibility

complex 1, or MHC class 1 for short. And immune cells called Natural Killer cells have proteins

on their surface that temporarily bind to these MHC class 1 proteins. In this case,

the Natural Killer displays a receptor, and the MHC class 1 is the ligand.  When that

happens, the cell is identified as part of your own body and the Natural Killer cell

leaves it alone. But when our cells are infected by viruses, say the chickenpox or herpes virus,

those MHC class 1s don’t get displayed anymore, and the Natural Killer cell destroys it. It’s

the ultimate version of not knowing the secret password. Ohh, you don’t have MHC? I guess

you’re gonna die then. Now, the cardiac gap junction and the Natural Killer cell examples

both depend on the cells touching each other. But what if you wanted to talk to cells a

little farther away? Well, it depends on how far away. If you want to communicate with

cells in the nearby — and just the nearby — vicinity, that’s where paracrine signaling

comes in handy. In this type of signaling, a cell will release a wave of ligands to the

liquid around itself, and potentially they run into receptors for that ligand. If not,

the ligand doesn’t exert an effect and gets broken down. You can see this in action whenever

you get a cut. When something disrupts the endothelium, that thin layer of epithelial

cells on the inside of a blood vessel, it releases chemicals into the bloodstream around

it. Those chemicals kick off a series of biological reactions that recruits platelets to the scene

of the injury. Those platelets stick together with other connective tissue on top of the

injury and provide the first steps to healing that cut. This is a great use of paracrine

signaling, since you only want the ligand to affect cells in the nearby area. It would

be bad news if all the platelets in your blood suddenly clumped together. So paracrine signaling

is a good way of communicating with nearby cells, but they can use some of the same mechanisms

to talk to themselves. It’s called autocrine signaling — a cell releases a ligand that

lands on a receptor it has on its own surface. It’s like writing yourself a message on

a sticky note in the morning and reading it at noon. We see this in a few different places,

mainly when it comes to tissues that are growing or differentiating like when we’re developing

in the womb. For instance, epithelial cells secrete a ligand called epithelial growth

factor that stimulates them to grow. But not every cell is cut out for autocrine signaling. This

type of communication relies on the cell having a lot of receptors on its surface that readily

bind to that ligand which makes them more likely to hear the message they just sent

out. We have one final way of communicating around the body, and it involves my favorite

chemicals, hormones. Endocrine signaling is what our endocrine system does, pumps hormones

into the bloodstream so it can land on a cell somewhere else in the body and have its effect.

Compared to all the other forms of communication, endocrine signaling is slow and by the time the hormone

gets to its receptor, it’s a weaker message compared to paracrine or autocrine signaling

where the ligands are more concentrated. So they’re slower, but their message lasts

longer and reaches more cells. And that’s exactly why we’d want to use them. Take

growth hormone, a hormone secreted by the pituitary gland that promotes the growth of

tissues like bone and cartilage. Clearly, we don’t just have a single patch of bone

tissue hanging out next to the pituitary gland, so paracrine signaling won’t work. By secreting

growth hormone into the blood, you make sure that lots of different tissue gets this chemical

message. Now, oftentimes endocrine signaling gets compared to a long distance call. And

while it’s true that hormones can travel a long distance through the bloodstream to

their target, that analogy isn’t perfect. It’s more like putting a bunch of messages

in bottles, and letting a river take them to your friends downstream. As you can see

from the few examples in this video, a ton of functions around the body depend on cell

communication to happen in a timely manner. One of them that we barely touched on in this

video was the immune response, a topic that requires some more attention. In the next

episode, we’ll discover how our immune cells learn how to fight off invading pathogens

and how they never forget. Thanks for watching this episode of Seeker Human. I’m Patrick Kelly.