Scientists Reverse Engineer Cellular Mechano-Chemical Feedback System – A Spiritual Insight

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Epithelial cells are a type of cell that lines the surfaces of your body. They are found on your skin, blood vessels, urinary tract, and organs. For example, the epithelial cell in urine test looks at urine under a microscope to see if the number of your epithelial cells is in the normal range,  and abnormal range can indicate a yeast or urinary tract infection (UTI), kidney or liver disease, or certain kinds of cancer. Recently researchers reported during the collective migration of epithelial cells, the migration direction is aligned over a tissue-scale expanse. [1] What is observed is collective movements of cells and the researchers are trying to understand how the cells communicate, i.e. cell migration is known to be directed by mechanical forces transmitted by cell-cell junctions, but it remains a mystery how the intercellular force transmission is coordinated with intracellular biochemical signaling to achieve the collective movements.  Every biological process requires some form of communication among cells not just with their neighbor cells, but also with those cells which are significantly farther away. The research group focused upon the MAPK/ERK or ERL pathway, and were able to demonstrate how the movement of a single cell could trigger a cascading reaction resulting in the migration of a cell collective. 

References

  1. Naoya Hino, Leone Rossetti, Ariadna Marín-Llauradó, Kazuhiro Aoki, Xavier Trepat, Michiyuki Matsuda and Tsuyoshi Hirashima, ERK-Mediated Mechanochemical Waves Direct Collective Cell Polarization, 3 June 2020, Developmental Cell, https://doi.org/10.1016/j.devcel.2020.05.011 

The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal begins when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division. The pathway includes many proteins, including MAPK (mitogen-activated protein kinases, originally called ERK, extracellular signal-regulated kinases), which communicate by adding phosphate groups to a neighboring protein (phosphorylating it), which acts as an “on” or “off” switch. When one of the proteins in the pathway is mutated, it can become stuck in the “on” or “off” position, which is a necessary step in the development of many cancers. Components of the MAPK/ERK pathway were discovered when they were found in cancer cells. Drugs that reverse the “on” or “off” switch are being investigated as cancer treatments.

These biochemical and mechanical signals in cells are a fundamental process controlling things such as homeostasis (the tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes), cell development, and disease. The MAPK/ERK pathway is so fundamental, it exists in all cells controlling a wide variety of actions from growth, development, and even cell death. The research team utilized a live imaging technique that was able to visualize an individual cell ERK activation. The imaging technique revealed how the cell pulls in the surrounding cells causing a sort of tug-of-war propagation which led to a collective movement.  Literature (previous papers) had stated that cells would push the surrounding cells, however, this visualization technique revealed the cells pull. A mathematical model was developed, and the researchers incorporated these observations into the model.  Running the model demonstrated a consistency with the experimental observation.  This paper [1] demonstrates that the ERK-mediated mechano-chemical feedback system generates complicated multicellular patterns. This provides a new basis for understanding many biological processes including tissue repair and tumor metastasis. The current understanding of the intercellular signal transduction mostly emphasized the importance of intercellular transfer of biochemical molecules including growth factors, hormones, and neurotransmitters. This present study raises another consideration, which is the critical role of cellular response to mechanical stimuli in intercellular signal transduction. There are three primary modes of intercellular communication, (i) direct contact between signaling molecules bound to the membranes of two adjacent cells, (ii) short-range soluble signals that diffuse over short distances, and (iii) long-range soluble signals that are secreted into the circulation to be carried anywhere in the body.

The Spiritual Insight that we receive from this type of research is related to the collective movements of cells where researchers are trying to understand how the cells communicate. We can see this application in the sense of how God communicates with us. The biblical examples of the Lord God communicating with people, we read how Adam conversed with God in the garden, how He told Noah to build an ark, and how He spoke to Moshe from a burning bush.  He promised Abraham a son, and even Paul heard him directly on the road to Damascus.  Often people wonder how the Lord communicates with us today, whether in an audible voice or in some other way.  The way we hear from the Lord God in heaven, just as we see in these biblical examples, may happen differently for different people.  There are nine ways in which the Lord God speaks to us according to the Scriptures.

  1. Through His Word (Torah, Prophets, Writings, and NT)
  2. Through the Messiah Yeshua, his life, his actions, and his words (Hebrews 1:1-2)
  3. Through Nature and God’s Creation (Romans 1:20)
  4. Through other faithful believers (James 3:17)
  5. Through praise and worship (2 Chronicles 20)
  6. Through circumstances (builds faith)
  7. Through His Holy Spirit (John 14:17, 1 Corinthians 3:16, i.e. the inner voice)
  8. Through prayer (Romans 8:26-27)
  9. Through dreams and/or visions (Joel 2:28)

What the Torah and Moshe, the prophets, and the writings teach us is how the Lord God speaks or communicates to His people. The Bible records the Lord God speaking audibly to people many times (Shemot / Exodus 3:14, Joshua 1:1, Judges 6:18, 1 Samuel 3:11, 2 Samuel 2:1, Job 40:1, Isaiah 7:3, Jeremiah 1:7, Acts 8:26 and 9:15).  There is no reason why the Lord would not speak to us in an audible voice today. There are different circumstances in which the Lord brings His purpose to our awareness.  This research paper [1] which reports on the collective movements of cells and how researchers are trying to understand how the cells communicate draws out these questions from the Scriptures and about our relationship with God. Note how the previous understanding was that cells push, whereas the new imaging technique reveal how cells pull. This parallels our relationship with God, he draws us, he does not push us. In biology, it seems to be a very complicated system.  In all of the ways in which God communicated with His people in the Bible, it is by means of getting His Word to those who need it.  This is why it is so important for us to read the Bible because God speaks to us through His Word (2 Timothy 3:16–17). The prophet Isaiah tells us in Isaiah 55:11 saying, “So is my word that goes out from my mouth: it will not return to me empty, but will accomplish what I desire and achieve the purpose for which I sent it.” (א   כֵּן יִהְיֶה דְבָרִי אֲשֶׁר יֵצֵא מִפִּי לֹא-יָשׁוּב אֵלַי רֵיקָם כִּי אִם-עָשָֹה אֶת-אֲשֶׁר חָפַצְתִּי וְהִצְלִיחַ אֲשֶׁר שְׁלַחְתִּיו:) We have God’s word today and we know what the Lord God wants in our lives! Peter wrote in 2 Peter 1:3 saying, “His divine power has given us everything we need for life and godliness through our knowledge of Him who called us by his own glory and goodness.”  The Scriptures states that we are to “walk in the instruction (Torah) of the Lord” (Tehillim / Psalms 119:1, אַשְׁרֵי תְמִימֵי-דָרֶךְ הַהֹלְכִים בְּתוֹרַת יְהֹוָה) meaning that we are to submit our lives to walking according to the instruction of God. This enables us to walk humbly with God. The instruction of God leads to repentance and turning from sin. In ancient Jewish thought the Torah was compared to the light, righteousness, justice, and truth. The following are a few examples from the Megillah, Midrash, and rabbinic commentary.

Megillah 16b:8מגילה ט״ז ב:ח׳

Rav Yehuda said: “Light”; this is referring to the Torah that they once again studied. And similarly it says: “For the mitzva is a lamp and the Torah is light” ….“Gladness” [simḥa]; this is referring to the Festivals that they once again observed. And similarly it says: “And you shall be glad [vesamakhta] on your Festival” .

Shemot Rabbah 34:2שמות רבה ל״ד:ב׳

Just as light came before all the deeds of Creation, as it is written “And E-lohim said ‘let there be light’ so too regarding the Tabernacle, in the Torah that is called light, as it is written ‘Because…a mitzvah is a candle and Torah is light’ , all the deeds came after the Torah.

Rabbeinu Bahya, Shemot 25:31:4רבנו בחיי, שמות כ״ה:ל״א:ד׳

A rational approach: The Menorah with its seven lamps is an allusion to the Torah which is generally known as אור, light. This is confirmed by the verse in Proverbs 20,27 we quoted earlier….Torah comprises seven different kinds of wisdoms . This is why the Menorah had seven lamps.

The Apostle Paul used rabbinic tradition to illustrate what Yeshua the Messiah had done for God’s people. He did this using midrash in 1 Corinthians 10:1-4.  This was a rabbinic midrash regarding the “rock that followed Israel in the wilderness” he used to illustrate this as being “the rock of Christ.” The Apostle Paul refers to Yeshua as the “Rock” that is also a term that was reserved for the Lord God Almighty according to the Torah in Parashat Ha’azinu. (see Devarim / Deuteronomy 32) King David said the Lord is his “rock of strength” (לְצוּר-מָעוֹז) and “You are my rock and my fortress” (כִּי-סַלְעִי וּמְצוּדָתִי אָתָּה) this illustrates how David saw the Lord God Almighty as a foundation stone upon which he stands, and Paul using this illustration in 1 Corinthians 10 with the help of the rabbinic midrash. The phrase, “…that followed them,” in the Apostolic Writings, comes from the Greek word, ἀκολουθούσης “akolouthouoses,” which means “to follow one who precedes, join him as his attendant, or accompany him.” (כִּי שָׁתוּ מִן הַצּוּר הָרוּחָנִי הַהוֹלֵךְ עִמָּהֶם) The Hebrew translation of ἀκολουθέω is הַהוֹלֵךְ which means to walk with. Notice how this spiritual rock (הַצּוּר הָרוּחָנִי) is walking with the people of God according to Paul’s use of the midrash. The Apostle Paul is explaining to the Corinthians that the “rock” at Meribah was spiritually patterned after Yeshua the Messiah. Using this example, Paul is saying that Yeshua walks alongside us with us in life and therefore he uses this parable to direct our attention to the Messiah. This is consistent with Paul’s reference to the Messiah being the purpose of the Torah. (Romans 10:4, הֲרֵי הַמָּשִׁיחַ הוּא תַּכְלִית הַתּוֹרָה) The Rock, who is God, was a figure or shadow, of the Messiah in a similar way that the Pesach lamb prefigured Yeshua. In addition to this, in the wilderness, the Rock was struck with the rod for the sake of Israel. Can you see the parallel here in the biblical text, with the parable of the rabbis and the things that Yeshua did for us? Yeshua suffered for our sakes (1 Peter 2:24) and he is the life giving waters (John 4:10, 7:37-39, and Revelation 22:17). What an awesome picture we see of Christ in the rabbinic literature and the words of the Apostle Paul in 1 Corinthians 10:1-4.  These things describe for us how important it is to study God’s Word, and how the Lord speaks to us through His Word!

Paul is explaining to us how Yeshua is the Messiah (Anointed one) in which we are to follow and believe upon (a very Torah centric principle). The good news of the Gospel, that which the people were taught in the wilderness (Hebrews 4:1-5), was the Lord dwelling in our midst, entering into our lives, helping us to live by faith as Paul wrote in Romans 10:5-6, מֺשֶׁה אָמְנָם כָּתַב עַל הַצְּדָקָה שֶׁמִּתּוֹךְ הַתּוֹרָה “אֲשֶׁר יַעֲשֶׂה אֺתָם הָאָדָם וָחַי בָּהֶם.” אַךְ כָּךְ אוֹמֶרֶת הַצְּדָקָה שֶׁמִּתּוֹךְ אֱמוּנָה, Paul said that Moshe wrote of the righteousness that is in the midst of the Torah, and quotes from the Torah saying “the man who does them will live by them.”  This suggests that it is possible to perform a command but not make it a part of our lives, a lifestyle thing (i.e. not “live by it.”) The context is to say that this is righteousness the comes by faith. Note how we are to live by faith, and this is the meaning of אֲשֶׁר יַעֲשֶׂה אֺתָם הָאָדָם וָחַי בָּהֶם, “the man who does them will live by them.”  Note the order of the Hebrew text, the emphasis is placed upon doing the command as it is first in the sentence. Throughout the Scriptures we are able to feel the heart of God and understand His desire, to have an intimate relationship with us.  These things speak to us about the purpose of God’s Word, to reveal to us His plan and desire to draw us near and help us through life.  The Torah was not given so man could simply jump through the right spiritual hoops. We are being told the Lord God Almighty, and His Messiah Yeshua, are leading us in His ways, not just our leading ourselves in His ways.

Paul wrote in Romans 1:20 saying, “For since the creation of the world (מֵאָז בְּרִיאַת הָעוֹלָם) God’s invisible qualities–his eternal power and divine nature–have been clearly seen, being understood from what has been made, so that men are without excuse.”  This speaks of studying God’s creation, just as we see the increasing complexity of cell communication, this reveals to us the magnificent beauty of all that God has made. We can see His creative hand! Even the ant, in his strength, and his storing up food all summer long, we learn of the wisdom God has programmed into His creatures. By studying the heavens (astronomy) we understand more of God’s greatness in His power via the vastness of the universe. In biology, we see His design in the miracle of death and rebirth (the biological cycle) the Lord God spoke these things into existence in the beginning. (Bereshit / Genesis 1-2)  

The Scriptures reveal to us how the Lord can speak to us through others as well, by a friend, a teacher, or a parent to convey His message of truth to us. These may be words of warning, just as Paul wrote in Romans 10:2 2 אֲנִי מֵעִיד עֲלֵיהֶם שֶׁיֵּשׁ לָהֶם קִנְאָה לֵאלֹהִים, אֲבָל קִנְאָה שֶׁאֵין עִמָּהּ דַּעַת that he warned / testified to his brethren about righteousness, one that is of God that comes by faith as opposed to one that is of one’s own making. What these things teach us is how the Lord God can speak to us in many ways. We have to be careful that we do not make God after our image in the sense that we believe he will speak and act only in a certain way. The Torah tells us that the Lord God Almighty is even able to speak through a donkey (Bamidbar / Numbers 22:28) as the donkey spoke to Bilam when Bilam would not listen to anyone else. We should expect the unexpected and be sensitive enough to hear His voice in others as the Spirit leads us.

The Lord can speak to us through worship, song, and circumstances.  Many times these are coupled in the sense that we are going through hard times and when praising the Lord He speaks to us through the words of the music.  What I am thinking of is in relation to depression and difficult times, praise music can lift our hearts and our souls. Music can be soothing and comforting that opens our heart to hear from the Lord.  An example from the Tanakh is from 2 Chronicles 20, King Jehoshaphat faced a huge army of enemies who could have easily destroyed His people, but he did a strange thing. With a declaration that his eyes were on God, he sent in a choir of praise singers as the Scriptures say, “Jehoshaphat appointed men to sing to the LORD and to praise him for the splendor of his holiness as they went out at the head of the army, saying: ‘Give thanks to the LORD, for his love endures forever’” (2 Chronicles 20:21, NIV).  Jehoshaphat was victorious because his intent was to give the glory to God seeking His help! 

Notice how though Moshe, the Lord God used the circumstances of plagues to speak to Pharaoh, not just through the plague, but also through the anointed one of God (Moshe). The request was to let the people go so that they could worship the Lord. The Scientific research on the collective movements of cells and how they communicate draws out these points about how the Lord is speaking to us. Those things that the Lord speaks to us through, His word, are as Isaiah states according to Isaiah 32:17 יז   וְהָיָה מַעֲשֵֹה הַצְּדָקָה שָׁלוֹם וַעֲבֹדַת הַצְּדָקָה הַשְׁקֵט וָבֶטַח עַד-עוֹלָם: 32:17 And the work of righteousness will be peace, And the service of righteousness, quietness and confidence forever. (NASB) Those who are God’s people are called to pursue justice and truth. This is why the Lord commanded that we appoint judges, such that there would be order and justice throughout the land. (See Devarim / Deuteronomy 16:18) When we pursue these things, in love and peace, our prayers will be heard. Remember that the Lord can speak to us through prayer as well, when we are praying, something is brought to mind to pray about concerning ourselves or others.  Peter wrote about something very significant according to 1 Peter 3:7 saying, “Husbands, in the same way be considerate as you live with your wives, and treat them with respect as the weaker partner and as heirs with you of the gracious gift of life, so that nothing will hinder your prayers.” Notice how a relationship with one’s wife can lead to whether our prayer is heard or not. This draws us back to the call for us to be merciful just as God is merciful, and to live in peace, and love one to another. If we do not have these things, or embrace these things, our prayers will not be heard. 

The one thing that is less talked about is how the Lord can speak to us through dreams and visions. One example we may take from the Scriptures is from Parashat Miketz (Bereshit / Genesis 41:1-44:17) and the life of Joseph. In the narrative, we read how Joseph had dreams, he told his dreams to his brothers and his parents and they did not like what he had to say. I have had dreams before when the Lord was speaking to me. I know others who have had the same. When sharing these things with some people, I have had them laugh at the matter not believing God can speak through dreams even though the scriptures say in the later days the Lord will do these this. (Joel 2:28, Acts 2:17) Later on, we read how Pharaoh has two dreams that deeply disturb him and he seeks a man who can interpret his dreams (41:1-13). Joseph is found to be an interpreter of dreams, and when called Joseph replies saying “It is not in me; God will give Pharaoh a favorable answer.” (וַיַּעַן יוֹסֵף אֶת-פַּרְעֹה לֵאמֹר בִּלְעָדָי אֱלֹהִים יַעֲנֶה אֶת-שְׁלוֹם פַּרְעֹה:) Joseph says that only God can give an answer of Shalom (שְׁלוֹם, peace) and then Joseph gives Pharaoh the interpretation from the Lord (41:16-38). Pharaoh recognized that God’s wisdom was in Joseph, so Pharaoh placed all of the power of Egypt into Joseph’s hands (41:39-46). The reality of the truth of God speaking to both Joseph and Pharaoh, seven years of plenty come and Joseph stores away the grain (41:46-53) and seven years of famine come and everyone buys food from him (41:54-42:6) including his brothers.  Joseph recognized the all powerful God, the all sufficient one (“El Shaddai,” אֵל שַׁדַּי) and Jacob also recognized the all sufficiency of God. There are other examples of the Lord speaking to people in dreams, Daniel (Daniel 7), Joseph in the NT, in Matthew 2:13, and Pontius Pilate’s wife according to Matthew 27:19.  The Scriptures describe how dreams were used by God to communicate His message to His people. The scientific research that speaks about the collective movements of cells where researchers are trying to understand how the cells communicate draws out the question of how God speaks to us. He draws us to Himself through His Word, and this Word of God is brought to us in many ways! Ultimately these things reveal to us how the Lord God in heaven is still speaking to us today, and all we have to do is listen to hear his voice!